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Brain tumors refer to abnormal cell proliferation formed in brain tissue, which can cause neurological dysfunction and cognitive impairment, posing a serious threat to human health. Therefore, it becomes a very challenging work to full-automaticly segment brain tumors using computers because of the mutual infiltration and fuzzy boundary between the focus areas and the normal brain tissue. To address the above issues, a segmentation method which integrates edge features is proposed in this paper. The overall segmentation architecture follows the encoder decoder structure, extracting rich features from the encoder. The first two layers of features are input to the edge attention module, and to extract tumor edge features which are fully fused with the features of the decoder segment. At the same time, an adaptive weighted mixed loss function is introduced to train the network by adaptively adjusting the weights of different loss parts in the training process. Relevant experiments were carried out using the public brain tumor data set. The Dice mean values of the proposed segmentation model in the whole tumor area (WT), the core tumor area (TC), and the enhancing tumor area (ET) reach 91.10%, 87.16%, and 88.86%, respectively, and the mean values of Hausdorff distance are 3.92, 5.12, and 1.92 mm, respectively. The experimental results showed that the proposed method can significantly improve segmentation accuracy, especially the segmentation effect of the edge part. [ABSTRACT FROM AUTHOR]

Defects and dysfunctions of temporomandibular joint (TMJ) disc are responsible for the majority of TMJ diseases. Current treatments in this matter are usually short-term and only palliative, thus an alternative treatment that offers long-lasting repair is in great demand. In recent years great attempts have been made to prepare an ideal scaffold, which best resembles the native TMJ disc in characteristics such as mechanical, physical and biological properties. This narrative review focuses on developments of the recent ten years in fabrication of scaffolds using decellularized tissues, natural and synthetic biomaterials for regeneration of TMJ disc and compared their properties. PubMed and Google Scholar data-bases were searched using the following keywords (“TMJ” OR “temporomandibular joint” OR “TMD” OR “temporomandibular disease”) AND (“scaffold” OR “hydrogels”). Randomized controlled trials, randomized clinical trials, case-controls, case reports, and animal studies were included. Comments, systematic reviews, meta-analyses, and non-English papers were excluded. The study concluded that hybrid scaffolds have exhibited favorable cell attachment and proliferation. Synthetic scaffolds have shown promise in providing better control over structural properties; however, additional processes are often required to provide biomimetic cell signaling. While there is still much to learn about the ideal scaffold for TMJ disc regeneration, both natural and synthetic scaffolds have shown promise in achieving the functional, structural, biological, and mechanical properties of a native TMJ disc. [ABSTRACT FROM AUTHOR]

The regulation of the cell cycle is essential for maintaining normal cellular function, especially in the development of diseases such as lung cancer. The cell cycle consists of four major phases (G1, S, G2 and M phases), which are characterized by a series of precise molecular events to ensure proper cell proliferation and division. In lung cancer cells, cell cycle dysregulation can lead to disordered proliferation and increased invasiveness of cancer cells. G2 and S-phase expressed 1 (GTSE1) is a regulatory protein found in the cytoplasm of the cell, which plays a key role in the cell cycle distribution of a wide range of cancer cells and is involved in life processes such as cell proliferation and apoptosis. GTSE1 affects cell cycle progression by interacting with cyclin-dependent kinase inhibitor 1A (p21) and maintaining the stability of p21, which in turn inhibits the activity of cyclin-dependent kinase 1/2 (CDK1/2). In addition, GTSE1 is also involved in the regulation of tumor protein 53 (p53) signaling pathway. With the assistance of mouse double minute 2 homolog (MDM2), GTSE1 is able to transport p53 from the nucleus to the cytoplasm and promote its ubiquitination and degradation, thus affecting cell cycle and cell deathrelated signaling pathways. This paper reviews the expression of GTSE1 in lung cancer cells and its effects on lung cancer, as well as its potential mechanisms involved in cell cycle regulation. [ABSTRACT FROM AUTHOR]

Chemokine-like factor-like MARVEL transmembrane domain containing member/chemokine-like factor superfamily member (CMTM/CKLFSF) including CKLF and CMTM -CMTM8 are a new family of proteins linking chemokines and transmembrane superfamilies. CMTM not only have broad chemotactic activities, but also associate with hematopoietic system, immune system, and tumor development and metastasis closely. CMTM proteins are involved in key biological processes of cancer development, which include activation and recycling of growth factor receptors, cell proliferation and metastasis, and regulation of the tumor immune microenvironment. This is a new focus of research on the relationship between CMTM and tumors, because CMTM4/CMTM6 can be considered as a regulator for programmed cell death ligand 1 (PD-L1). This paper reviews the role of CMTM family members on cancer, especially in tumor growth, metastasis and immune escape, summarize the latest findings on the relationship between CMTM and non-small cell lung cancer, and explores the potential clinical value of CMTM as a novel drug target or biomarker. [ABSTRACT FROM AUTHOR]

Background : Skeletal muscle mishaps are the most well-known incidents in society, especially among athletes and the military population. From the various urgency, this accident needs to be cured more quickly. However, the current treatment still has some shortcomings and is less effective. In this case, Paired box 3 and Paired box 7 (Pax3/Pax7) proteins that induce stem cells could potentially be an alternative treatment for skeletal muscle injuries. This paper aimed to analyse the potential treatment of Pax3/Pax7 proteins inducing the stem cell for skeletal muscle injuries. We did a narrative review by gathering several scientific journals from several leading platforms like PubMed and Scopus. As common accidents, skeletal muscle disease could be due to workplace and non-workplace causes. The highest risk occurs in the athlete and military environment. The treatment of current skeletal muscle injuries is protection, rest, ice, compression, and elevation (PRICE), non-steroidal anti-inflammatory drugs (NSAIDs), and mechanical stimulation. However, it is considered less effective, especially in NSAIDs, inhibiting myogenic cell proliferation. The current finding indicates that the stem cells have markers known as Pax3/Pax7. The role of both markers in muscle injury, Pax3/Pax7, as transcription factors will induce cell division by H3K4 methylation mechanisms and chromatin modifications that stimulate gene activation. Conclusion: Regulation by Pax3/Pax7 factors that affect stem cells and stem cell proliferation is one of the alternative treatments. This regulation can accelerate the healing of injury victims, especially injuries to the skeletal muscles. Finally, after being compared, Pax3/Pax7 induces stem cells to have the potential to be one of the skeletal muscle injury treatments. Keywords: Pax3 and Pax7, Pax3/Pax7, Skeletal muscle, Athlete, Stem cells, Cell proliferation, Injuries. [ABSTRACT FROM AUTHOR]

Close to half of human cancers harbor point mutations in the tumor-suppressor p53 gene, giving rise to the cellular accumulation of mutant p53 (mutp53) proteins with novel neomorphic gain-of-function (GOF) properties. The destruction of mutp53 proteins through either autophagic or proteasomal degradation is a viable strategy for the targeted therapy of p53-mutated cancers. Several nanomaterials, including zinc-iron and ZIF-8 nanoparticles (NPs), have been reported to induce the proteasomal degradation of mutp53 proteins. However, how autophagy, the other major cellular degradative pathway, influences NP-induced mutp53 degradation has not been investigated. This article shows that AIE-Mit-TPP, a mitochondria-targeting material with aggregation-induced emission (AIE) characteristics, elicits ubiquitination-dependent proteasomal degradation of a broad range of mutp53 proteins. Meanwhile, AIE-Mit-TPP also induces massive mitochondrial damage and autophagy. The inhibition of autophagy further increases AIE-Mit-TPP-elicited mutp53 degradation, revealing the negative impact of autophagy on AIE-Mit-TPP-induced mutp53 degradation. As expected, the degradation of mutp53 proteins by AIE-Mit-TPP abrogated mutp53-manifested GOF, leading to reductions in cell proliferation and migration and increases in cell cycle arrest and cell death. Consequently, AIE-Mit-TPP inhibited the growth of mutp53 tumors. This paper unravels the interesting interplay between the proteasomal and autophagic degradative pathways and pinpoints the modulation of autophagy as a potential strategy for optimizing NP-induced mutp53 degradation and p53-targeted cancer therapy. We have designed three different types of AIE materials: non-targeting (AIE-Br), mitochondria-targeting (AIE-Mit-TPP), lysosome-targeting (AIE-Lyso). Our results proved that mitochondria-targeting AIE material induced degradation of mutp53 proteins via the proteasome degradation pathway and abrogated mutp53-conferred GOF phenotypes. Furthermore, we performed in vitro studies on the effect of the tested materials in mutp53-expressing cancer cells and demonstrated our findings via in vivo investigations in a mouse subcutaneous p53R175H TOV112D ovarian cancer model. Our results confirmed the link between the proteasome pathway and autophagy and thus proposed a strategy of combining AIE-Mit-TPP with autophagy inhibitors for the targeted treatment of mutp53-associated tumors. Finally, we found that AIE-Mit-TPP could induce degradation of a wide-spectrum mutp53 proteins, which makes mitochondria-targeting AIE materials an effective therapeutic strategy for p53-mutated cancers. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The prognosis of wild-type BRAF cutaneous melanoma (WT Bf-CM) patients remains poor due to the lack of therapeutic options. However, few studies have investigated the factors contributing to the prognosis of WT Bf-CM patients. Methods: In this paper, we proposed and validated a novel 7-RNA based signature to predict the prognosis of WT Bf-CM by analyzing the information from TCGA database. Results: Dependence of this signature to other clinical factors were verified and a nomogram was also drawn to promote its application in clinical practice. Functional analysis suggested that the predictive function of this signature might attribute to the prediction of the up-regulation of RNA splicing, transcription, and cellular proliferation in the high-risk group, which have been demonstrated to be linked to malignancy of cancer. Moreover, functional analysis and therapy response analysis supported that the prognosis is highly related to PI3K/Akt/mTOR pathway among WT Bf-CM patients. Conclusion: Collectively, this study will provide a preliminary bioinformatics evidence for the molecular mechanism and potential drug targets that could improving WT Bf-CM prognosis. [ABSTRACT FROM AUTHOR]

Abstract Environmental chemicals such as phthalate esters may have adverse effects on anogenital distance (AGD), but the evidence in both genders has not been reviewed systematically. The objective of the present study is to conduct a systematic review and meta-analysis of studies that analyzed the relationship between exposure to phthalates and AGD. English papers published up to March 2018 were searched in PubMed, Scopus, Clarivate-Web of Science, and Google scholar. We applied fixed-effects models to calculate pooled beta coefficient [β]. In the case of heterogeneity, random-effects models were used. Using the comprehensive search strategies, 313 papers were identified and after screening, 10 of them were included in this study. In primary analyses, we found that exposure to phthalates was not associated with short AGD (β = −0.11; 95% CI, −0.27, 0.06; I2 = 0%). However, results of subgroup analyses indicated that in boys, the sum of di-2-ethylhexyl phthalate (∑DEHP) metabolites had significant association with the risk of shortened anopenile distance (AGD AP) (β = −0.915, 95% CI: 1.629, −0.2) and anoscrotal distance (AGD AS) (β = −0.857, 95% CI: 1.455, −0.26). In addition, urinary monobutyl phthalate (MBP), monoethyl phthalate (MEP), and monoisobutyl phthalate (MiBP) were associated with short AGD AP. We also observed significant association between monobenzylphthalate (MBzP) and anofourchette distance (AGD AF) in girls. Our study provided findings on significant association of exposure to ∑DEHP metabolites, MBP, MEP, and MiBP with shortened AGD AP in boys. The mechanisms of phthalates effect on AGD may involve receptors and enzymes involved in steroidgenesis, negative influence on Leydig cells, cell proliferation, gonocyte cell numbers, and testosterone production. Graphical abstract Image 1 Highlights • Sum of ∑DEHP metabolites had significant association with the risk of shortened AGD AP and AGD AS. • Monobutyl phthalate (MBP), monoethyl phthalate (MEP), and monoisobutyl phthalate (MiBP) were associated with short AGD AP. • There is a significant relationship between monobenzylphthalate (MBzP) and AGD AF in girls. [ABSTRACT FROM AUTHOR]

As one of the most lethal diseases, pancreatic cancer shows a dismal overall prognosis and high resistance to most treatment modalities. Furthermore, pancreatic cancer escapes early detection during the curable period because early symptoms rarely emerge and specific markers for this disease have not been found. Although combinations of new drugs, multimodal therapies, and adjuvants prolong survival, most patients still relapse after surgery and eventually die. Consequently, the search for more effective treatments for pancreatic cancer is highly relevant and justified. As a newly re-discovered mediator of gasotransmission, hydrogen sulfide (H 2 S) undertakes essential functions, encompassing various signaling complexes that occupy key processes in human biology. Accumulating evidence indicates that H 2 S exhibits bimodal modulation of cancer development. Thus, endogenous or low levels of exogenous H 2 S are thought to promote cancer, whereas high doses of exogenous H 2 S suppress tumor proliferation. Similarly, inhibition of endogenous H 2 S production also suppresses tumor proliferation. Accordingly, H 2 S biosynthesis inhibitors and H 2 S supplementation (H 2 S donors) are two distinct strategies for the treatment of cancer. Unfortunately, modulation of endogenous H 2 S on pancreatic cancer has not been studied so far. However, H 2 S donors and their derivatives have been extensively studied as potential therapeutic agents for pancreatic cancer therapy by inhibiting cell proliferation, inducing apoptosis, arresting cell cycle, and suppressing invasion and migration through exploiting multiple signaling pathways. As far as we know, there is no review of the effects of H 2 S donors on pancreatic cancer. Based on these concerns, the therapeutic effects of some H 2 S donors and NO–H 2 S dual donors on pancreatic cancer were summarized in this paper. Exogenous H 2 S donors may be promising compounds for pancreatic cancer treatment. The review summarizes the antitumor mechanisms of H 2 S donating derivatives against pancreatic cancer by modulating signaling pathways, including PI3K/AKT/mTOR, SHH, NF- κ B, MAPK, NOTCH, STAT3, DR4, etc. Perspectives on future directions and challenges are also discussed. [Display omitted] [ABSTRACT FROM AUTHOR]

With the deepening of research, proteomics has developed into a science covering the study of all the structural and functional characteristics of proteins and the dynamic change rules. The essence of various biological activities is revealed from the perspectives of the biological structure, functional activity and corresponding regulatory mechanism of proteins by proteomics. Among them, phospholipid-binding protein is one of the hotspots of proteomics, especially annexin A1, which is widely present in various tissues and cells of the body. It has the capability of binding to phospholipid membranes reversibly in a calcium ion dependent manner. In order to provide possible research ideas for researchers, who are interested in this protein, the biological effects of annexin A1, such as inflammatory regulation, cell signal transduction, cell proliferation, differentiation and apoptosis are described in this paper. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is one of the malignant tumors with highest mortality in the world, it is still a difficult problem in clinical field. Its occurrence and development are closely associated with tumor angiogenesis. Angiopoietin-2 (Ang-2) is an important angiogenesis factor that has involved in many researches and it has been confirmed that the expression of Ang-2 is significantly up-regulated in tissues and blood of NSCLC. Meanwhile, Ang-2 is related to malignant biological behavior of cancer cells, making it a potential biological marker for the diagnosis and prognosis of NSCLC. At present, researches on Ang-2 how to promote the progression of NSCLC around the world are focused on Ang-2 regulating the proliferation, invasion, and metastasis of NSCLC. This paper summarized and estimated the studies and literature reports of regulatory mechanisms of Ang-2 in NSCLC, hopefully it could help looking for targeted drug treatment of Ang-2 in the future. [ABSTRACT FROM AUTHOR]

Interfacing neurons with graphene, a single atomic layer of sp 2 hybridized C-atoms, is a key paradigm in understanding how to exploit the unique properties of such a two-dimensional system for neural prosthetics and biosensors development. In order to fabricate graphene-based circuitry, a reliable large area patterning method is a requirement. Following a previously developed protocol, we monitored the in vitro neuronal development of geometrically ordered neural network growing onto patterned Single Layer Graphene (SLG) coated with poly-D-lysine. The microscale patterns were fabricated via laser micromachining and consisted of SLG stripes separated by micrometric ablated stripes. A comprehensive analysis of the biointerface was carried out combining the surface characterization of SLG transferred on the glass substrates and Immunohistochemical (IHC) staining of the developing neural network. Neuronal and glial cells proliferation, as well as cell viability, were compared on glass, SLG and SLG-patterned surfaces. Further, we present a comparative developmental study on the efficacy of synaptic transmission on control glass, on transferred SLG, and on the micropatterned SLG substrates by recording miniature post synaptic currents (mPSCs). The mPSC frequencies and amplitudes obtained on SLG-stripes, SLG only and on glass were compared. Our results indicate a very similar developmental trend in the three groups, indicating that both SLG and patterned SLG preserve synaptic efficacy and can be potentially exploited for the fabrication of large area devices for neuron sensing or stimulation. Statement of significance This paper compares the morphological and functional development of neural networks forming on glass, on Single Layer Graphene (SLG) and on microsized patterned SLG substrates after neuron spontaneous migration. Neurons developing on SLG are viable after two weeks in vitro, and, on SLG, glial cell proliferation is enhanced. The functionality of the neural networks is demonstrated by measuring the development of neuron synapses in the first and second week in vitro. Preserving the neuron synaptic efficacy, both homogeneous and patterned interfaces based on graphene can be potentially exploited for the fabrication of large area devices for neuron sensing or stimulation, as well as for next generation of bio-electronic systems, to be used as brain-interfaces. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the development of an automated umbilical cord blood (UCB) collection instrument, comprising of mechanical, electronics and control components, is provided in detail. UCB from the placenta provides a rich source of highly proliferative cells for many clinical uses as it contains rich Hematopoietic Stem Cells (HSCs) which yield many benefits over traditional sources such as the bone marrow and periphery blood. Current collection of UCB uses a syringe to extract blood from placenta, which is highly limited in volume and cell numbers. This paper will present the development of an automated UCB collection instrument to yield improved performance which comprised four subsystems. First, a placenta handling system is designed to produce air pressure which can realize the emulation of the uterus compression on the placenta. Second, an auto-medium injector system is presented to enable perfusion automatically. Third, a time window widening system is developed which generates vibrations during the perfusion phase and helps the exposed end of the cord cool down to a low temperature. Finally, a control platform is used to integrate all systems working together, hosting the control algorithms which operate the instrument automatically. [Copyright &y& Elsevier]

The article presents several papers related to urinary and reproductive system cancer. One of the paper suggests that small molecule transforming growth factor (TGFb1) receptor kinase inhibitors like LY2109761 are good candidates for prostate cancer clinical trials. Another study was conducted to study the clinicopathological characteristics of Lynch syndrome-associated endometrial carcinoma in China. Another study was conducted by Lizhi Zhang and colleagues to explore the role of extracellular signal regulated kinase (ERK) signal pathway in insulin-induced proliferation promotion, apoptosis inhibition and invasion promotion in endometrial cancer cells.

This paper discusses the combination of a Gene Regulatory Network (GRN) with a Genetic Algorithm (GA) in the context of spatial proliferation of artificial and dynamical cells. It gives the first steps in constructing and investigating simple ways of self-adaptation to furnish lifelike behaving cells. We are thus interested in growing an adaptive cells population in respect to environmental conditions. From a single cell, evolving on some nutriment field, we obtain relatively complex shapes, and functions, acquired with a GA. In a previous work, the artificial cells have been implemented with physical primitives for motion (in order to move correctly in space by convection and diffusion dynamics). The main goal of this current work is therefore to implement, for these physically moving cells, an embedded mechanism providing them with decisions capacities when it comes to choose the suitable “biological” routines (mitosis, apoptosis, migration…) depending on nutriment conjuncture. To that end, we use a “protein-based” GRN, "easily" evolvable to achieve adequate behavior in response to environment inputs. In order to build such a GRN, we start from random GRNs, train them using a GA with a generic nutriment field and different fitness functions, and finally we run the obtained evolved GRN in different nutriment fields to test the robustness of our self-adaption structure. [ABSTRACT FROM AUTHOR]

One of the major challenges facing researchers of tissue engineering is the scaffold design with desirable physical and mechanical properties for growth and proliferation of cells and tissue formation. In this paper, firstly, β-tricalcium phosphate (β-TCP) nanopowders with particle size of 50-70 nm were synthesized using a simple sol-gel route with calcium nitrate and potassium dihydrogenphosphate as calcium and phosphorus precursors, respectively. Then, the porous ceramic scaffold containing 40, 50, and 60 wt% of nβ-TCP was prepared by the polyurethane sponge replication method. The scaffolds were coated with P3HB for 30 sec and 1 min in order to increase the scaffold's mechanical properties. XRD, XRF, SEM, TEM, and FT-IR were used in order to study the phase and element structure, morphology, particle size, and determination of functional groups, respectively. Based on the results of compressive strength and porosimetry tests, the most appropriate type of scaffold is 50 wt% of nβ-TCP immersed for 30 sec in P3HB with 75% porosity in 200-600 μm, with a compressive strength of 1.09 MPa and a compressive modulus of 33 MPa, which can be utilized in bone tissue engineering. [ABSTRACT FROM AUTHOR]

In this paper, we present further work on the influence of minor additions of Ru to the Ti–20Nb alloy system, with a primary focus on mechanical properties of the as-cast material, along with microstructural response to elevated temperatures. Findings include high as-cast strengths and admissible strain values, up to 920 MPa and 1.5% respectively, along with moduli down to approximately 65 GPa in the as-cast state. Together with a significant increase in cell proliferation under MTS assay relative to controls, this indicates the chosen alloy system has significant promise for application in porous orthopaedic biomaterials, in particular those alloys with 0.5–1.0% Ru are deemed most suitable. Given their promise, preliminary investigation of the alloy system’s response to thermal treatment was also undertaken. Statement of Significance The presented research, an investigation into the mechanical properties and response to thermal treatments of Ru-containing Ti–20Nb-base alloys, holds significance in the field of metallic biomaterials due to the heretofore limited investigation into the impact of Ru on the properties of biomedical, β -phase, Ti-based alloys. Given Ru’s known beneficial impact on corrosion resistance, experimental confirmation of the impact of addition on mechanical properties was needed; that suitable mechanical properties, including yield strengths up to ∼930 MPa along with elastic admissible strains approaching 1.5%, were achieved is both promising in and of itself, and of significant note for further research into the field. Preliminary thermal and cell-proliferation studies are additionally provided to inform further studies. [ABSTRACT FROM AUTHOR]

Non-destructive protocols which can define a biomaterial’s degradation and its associated ability to support proliferation and/or promote extracellular matrix deposition will be an essential in vitro tool. In this study we investigate fluorescently tagged biomaterials, with varying rates of degradation and their ability to support cell proliferation and osteogenic differentiation. Changes in fluorescence of the biomaterials and the release of fluorescent soluble by-products were confirmed as accurate methods to quantify degradation. It was demonstrated that increasing rates of the selected biomaterials’ degradation led to a decrease in cell proliferation and concurrently an increase in osteogenic matrix production. A novel turnover index (TI), which directly describes the effect of degradation of a biomaterial on cell behaviour, was calculated. Lower TIs for proliferation and high TIs for osteogenic marker production were observed on faster degrading biomaterials, indicating that these biomaterials supported an upregulation of osteogenic markers. This TI was further validated using an ex vivo chick femur model, where the faster degrading biomaterial, fibrin, led to an increased TI for mineralisation within an epiphyseal defect. This in vitro tool, TI, for monitoring the effect of biomaterial degradation on extracellular matrix production may well act as predictor of the selected biomaterials’ performance during in vivo studies. Statement of Significance This paper outlines a novel metric, Turnover Index (TI), which can be utilised in tissue-engineering for the comparison of a range of biomaterials. The metric sets out to define the relationship between the rate of degradation of biomaterials with the rate of cell proliferation and ECM synthesis, ultimately allowing us to tailor material for set clinical requirements. We have discovered some novel comparative findings that cells cultured on biomaterials with increased rates of degradation have lower rates of proliferation but alternatively have a greater production of osteogenic markers compared to materials which degrade slower. By making comparisons in a rigorous manner, we can begin to define a useful matrix for materials which ultimately may aid for clinical selection. [ABSTRACT FROM AUTHOR]

Mg and its alloys are used in various application areas, where the wetting property is a special requirement. For example, surface wettability of a biomaterial plays a vital role in cell adhesion and proliferation. In this context, rare earth Mg alloy (WE54), a potential biomaterial, was studied to examine its wetting behavior. In order to tailor the surface properties, laser surface melting (LSM), a single process method, was adopted. In this paper, the effective change on wettability properties of WE54 after LSM process was studied under deionized water and simulated body fluid. A 500 watt nanosecond pulse Nd:YAG laser having a wavelength of 1064 nm was used to modify surface properties. Microstructure and surface morphology were examined by scanning electron microscope and profilometer, respectively. Cellular structure and some buds were observed on the laser melted surface of WE54. Evaporation of Mg and enrichment of Y up to 12.10% and 13.43% were observed. The contact angle was reduced from 81 o to 41.03 o in deionized water after laser treatment, whereas in SBF solution it was reduced to 23.13 o . It indicates that WE54 alloy also has a bio-wettability characteristic, which is very important for bio-applications. [ABSTRACT FROM AUTHOR]

MicroRNAs species are short, noncoding RNAs formed of 19–24 nucleotides. MicroRNAs play an essential role in the regulation of the humoral biochemical processes, cellular proliferation, or other biological processes in the human body. Tissue injuries, biochemical dysfunction, and physiological imbalances are followed by a significant change in the expression of microRNAs in biological fluids. With the recent advances in bioanalysis techniques, it is now possible to identify the microRNA species in biological fluids in specific situations for polytrauma patients. In this paper, we present the importance and the clinical significance of using microRNAs as diagnostic biomarkers for critically ill polytrauma patients. [ABSTRACT FROM AUTHOR]

This paper aims to study the effect of telomerase inhibitors zidovudine (AZT) on cell morphology, survival rate and telomerase activity of in-vitro culture myeloma cell line (U266).It has provided experiment basis for applying telomerase inhibitors in multiple myeloma treatment. The myeloma cellline in logarithmic phase (U266) could be divided into AZT group and negative control group, which are added with 100 µL AZT respectively and diluted into different concentrations with culture solution (1,10,100 and 1000 µmol-L-¹) of AZT, as well as culture solution of the same volume. After cultivating for 24, 48, 72 h, morphological changes of U266 cell is observed under optical microscope. Survival rate of cell is detected with MTT method, the change of telomerase activity is detected with TRAP-PCR-ELISA method. There is significant change in U266 cell morphology after AZT effect, their volume has been smaller and shrunken. Its shape has changed from short spindle to polygon or irregular shape, and broken away from the neighboring cells. Through comparing with control group, the survival rate of U266 cell in AZT group has decreased significantly (P<0.05), it represents time and concentration dependence. Median lethal concentration of AZT on U266 cell (IC50) is 1000µmol-L-¹.The drop in telomerase-activity has decreased by 55.74% (P<0.05) through applying 1000 µmol-L-¹ AZT on U266 cell for 72 h. AZT has significant inhibiting effect on the proliferation of myeloma cell line, and could reduce the telomerase activity of myeloma cell. [ABSTRACT FROM AUTHOR]

Abstract: Absorbent points widely used in endodontic therapy were transformed into bioresorbable chlorhexidine delivery systems for the treatment of the periodontal pocket by preventing its recolonization by the subgingival microflora. These paper points (PPs) were first oxidized to promote their resorption, then grafted with β-cyclodextrin (CD) or maltodextrin (MD) in order to achieve sustained delivery of chlorhexidine. We investigated the oxidation step parameters through the time of reaction and the nitric and phosphoric acid ratios in the oxidizing mixture, and then the dextrin grafting step parameters through the time and temperature of reaction. A first selection of the appropriate functionalization parameters was undertaken in relation to the degradation profile kinetics of the oxidized (PPO) and oxidized–grafted samples (PPO-CD and PPO-MD). Samples were then loaded with chlorhexidine digluconate (digCHX), a widely used antiseptic agent in periodontal therapy. The release kinetics of digCHX from PPO-CD and PPO-MD samples were compared to PP, PPO and to PerioChip® (a commercial digCHX containing gelatine chip) in phosphate buffered saline (pH 7.4) by ultraviolet spectrophotometry. The cytocompatibility of the oxidized–grafted PP was demonstrated by cell proliferation assays. Finally, the disc diffusion test from digCHX loaded PPO-MD samples immersed in human plasma was developed on pre-inoculated agar plates with four common periodontal pathogenic strains: Fusobacterium nucleatum, Prevotella melaninogenica, Aggregatibacter actinomycetem comitans and Porphyromonas gingivalis. To conclude, the optimized oxidized-dextrin-grafted PPs responded to our initial specifications in terms of resorption and digCHX release rates and therefore could be adopted as a reliable complementary periodontal therapy. [Copyright &y& Elsevier]

Abstract: Scaffolds with a high surface-area-to-volume ratio (SA:V) are advantageous with regard to the attachment and proliferation of cells in the field of tissue engineering. This paper reports on the development of novel melt-spun fibers with a high SA:V, which enhanced the surface effects of a fiber-based scaffold while maintaining its mechanical strength. The cross-section of the fibers was altered to a non-circular shape, producing a higher SA:V for a similar cross-sectional area. To obtain fibers with non-circular cross-sectional shape, or shaped fibers, three different types of metal spinnerets were fabricated for the melt-spinning process, each with circular, triangular or cruciform capillaries, using deep X-ray lithography followed by nickel electroforming. Using these spinnerets, circular and shaped fibers were manufactured with biodegradable polyester, polycaprolactone. The SA:V increase in the shaped fibers was experimentally investigated under different processing conditions. Tensile tests on the fibers and indentation tests on the woven fiber scaffolds were performed. The tested fibers and scaffolds exhibited similar mechanical characteristics, due to the similar cross-sectional area of the fibers. The degradation of the shaped fibers was notably faster than that of circular fibers, because of the enlarged surface area of the shaped fibers. The woven scaffolds composed of the shaped fibers significantly increased the proliferation of human osteosarcoma MG63 cells. This approach to increase the SA:V in shaped fibers could be useful for the fabrication of programmable, biodegradable fiber-based scaffolds in tissue engineering. [Copyright &y& Elsevier]

Abstract: Objectives: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at a post-transcriptional level. Through binding to mRNA sequences, miRNAs have a wide variety of functions, and are key regulators in vascular disease. Although there are only 2 papers looking directly at the association between miRNA and abdominal aortic aneurysms (AAA), several studies have looked at miRNAs implicated in vascular smooth muscle cell (VSMC) proliferation, extracellular matrix (ECM) remodelling, and the known genes and genetic loci associated with AAA. This review aims to determine potential miRNAs associated with the pathways involved in abdominal aortic aneurysm (AAA) pathophysiology, to guide future focused research. Methods and results: A systematic review of the published literature was performed, searching for articles detailing miRNA associations with AAA or processes associated with aneurysm formation. Eighteen miRNAs were identified to be associated with aneurysm formation, ten miRNAs were associated with VSMC physiology, and nine miRNAs were involved in regulation of the ECM. Seven miRNAs were replicated in more than 1 study (miR-19b, miR-21, miR-26a, miR-29b, miR-146a, miR-221, miR-222). Conclusions: The association between miRNAs associated with known AAA genes, and those involved in VSMC/ECM pathophysiology highlight promising areas for further significantly powered human studies, which with miRNA level modulation, present a novel opportunity to determine pathways for AAA formation. [Copyright &y& Elsevier]

Abstract: Recombinant proteins represent a new and promising class of polymeric materials in the field of biomaterials research. An important model for biomaterial design is elastin, the protein accounting for the elasticity of several tissues. Human elastin-like polypeptides (HELPs) have been developed as recombinant versions of elastin with the purpose of enhancing some peculiar characteristics of the native protein, like self-assembling. In this paper, we report on a comparative study of rat myoblasts response to coatings based on two different HELP macromolecules, with respect to control cultures on bare cell culture polystyrene and on a standard collagen coating. Cell behavior was analyzed in terms of adhesion, proliferation and differentiation. The collected data strongly suggest the use of HELPs as excellent biomaterials for tissue engineering and regenerative medicine applications. [Copyright &y& Elsevier]

Abstract: The use of microstructured substrates to study and influence cell orientation, which plays an important role in tissue functionality, has been of great interest lately. Silicon and poly(dimethylsiloxane) substrates have typically been used, but long processing times and exogenous protein surface coating, required to enhance cell viability, limit their use as large-scale platforms. There is thus a need for a non-biodegradable biocompatible substrate that allows rapid and low cost microfabrication. In this paper a styrene–(ethylene/butylene)–styrene block co-polymer (SEBS) microstructured by a rapid replication technique using low pressure an isothermal hot embossing approach has been demonstrated. SEBS substrates were treated with oxygen plasma to enhance cell adhesion and sterilized using ethylene oxide gas. While cell adhesion to and proliferation on these substrates was as good as on tissue culture polystyrene, cellular alignment on microstructured SEBS was also very high (97.7±0.5%) when calculated within a 10° angle variation from the longitudinal axis. Furthermore, tissue sheets on microstructured SEBS have been produced and exhibited cellular alignment within the engineered tissue. In addition, these results were obtained without coating the material with exogenous proteins. Such substrates should be helpful in the culture of tissue engineered substitutes with an intrinsic orientation and to elucidate questions in cell biology. [Copyright &y& Elsevier]

Abstract: Despite many synthetic biomaterials having physical properties that are comparable or even superior to those of natural body tissues, they frequently fail due to the adverse physiological reactions they cause within the human body, such as infection and inflammation. The surface modification of biomaterials is an economical and effective method by which biocompatibility and biofunctionality can be achieved while preserving the favorable bulk characteristics of the biomaterial, such as strength and inertness. Amongst the numerous surface modification techniques available, plasma surface modification affords device manufacturers a flexible and environmentally friendly process that enables tailoring of the surface morphology, structure, composition, and properties of the material to a specific need. There are a vast range of possible applications of plasma modification in biomaterial applications, however, the focus of this review paper is on processes that can be used to develop surface morphologies and chemical structures for the prevention of adhesion and proliferation of pathogenic bacteria on the surfaces of in-dwelling medical devices. As such, the fundamental principles of bacterial cell attachment and biofilm formation are also discussed. Functional organic plasma polymerised coatings are also discussed for their potential as biosensitive interfaces, connecting inorganic/metallic electronic devices with their physiological environments. [Copyright &y& Elsevier]

Abstract: This paper reports a new method of cross-linking electrospun zein fibers using citric acid as a non-toxic cross-linker to enhance the water stability and cytocompatibility of zein fibers for tissue engineering and other medical applications. The electrospun structure has many advantages over other types of structures and protein-based biomaterials possess unique properties preferred for tissue engineering and other medical applications. However, ultrafine fiber matrices developed from proteins have poor mechanical properties and morphological stability in the aqueous environments required for medical applications. Efforts have been made to improve the water stability of electrospun protein scaffolds using cross-linking and other approaches, but the current methods have major limitations, such as cytotoxicity and low efficiency. In this research electrospun zein fibers were cross-linked with citric acid without using any toxic catalysts. The stability of the cross-linked fibers in phosphate-buffered saline and their ability to support the attachment, spreading and proliferation of mouse fibroblast cells were studied. The cross-linked electrospun fibers retained their ultrafine fibrous structure even after immersion in PBS at 37°C for up to 15days. Citric acid cross-linked electrospun zein scaffolds showed better attachment, spreading and proliferation of fibroblast cells than uncross-linked electrospun zein fibers, cross-linked zein films and electrospun polylactide fibers. [ABSTRACT FROM AUTHOR]

Abstract: This paper investigates the role of microtopographical features on the cytomorphology, alignment, proliferation and gene expression of tenocytes. We made use of simple microfabrication approaches to create surfaces patterned with topographical features suitable for in vitro studies of tenocytes. These surfaces were composed of glass substrates patterned with polymeric ridges spaced from 50 to 250μm apart. Our studies demonstrate that the microgrooves differentially impact tenocyte shape, alignment and matrix organization along the direction of grooves. Groove widths significantly influenced cellular alignment, with 50μm grooved patterns affecting alignment most substantially. Polarized light microscopy demonstrated that mature collagen fibers were denser and more oriented within 50μm patterns. None of the patterns had a significant effect on the expression of genes linked to proliferation or extracellular matrix synthesis, although time in culture profoundly influenced both gene groups. COMP mRNA expression was moderately increased in tenocytes seeded onto 250μm grooves, but there was no overall beneficial phenotypic effect of aligned growth. The results of this study indicate that microtopography affects cell density and alignment of tenocytes and leads to the deposition of an aligned collagen matrix, but does not significantly impact matrix gene expression or cell phenotype. These outcomes provide insights into the biology of tendon regeneration, thus providing guidance in the design of clinical procedures for tendon repair. [Copyright &y& Elsevier]

Feline eyelid hidrocystoma is a rarely reported disease of the apocrine glands of Moll that has been variably interpreted as proliferative/neoplastic lesion or retention cyst. The purpose of this paper was to investigate feline hidrocystoma pathogenesis by means of a histological and immunohistochemical study. Nine paraffin embedded biopsies of eyelid hidrocystoma were retrieved from our archives. Histological sections were immunostained with antibodies anti-cytoskeletal proteins and Ki67 antigen. All hidrocystomas were observed in Persian cats, seven males/two females, mean age 9.6 years. Histologically, single or multiple, variably sized cysts expanded eyelid dermis. Cyst was lined by cuboidal epithelium, occasionally raising in papillary structures. Immunostaining was consistent with apocrine gland epithelium (cytokeratin 8/18; 19 and 14 positive). Ki67 immunolabelled nuclei ranged from 5.3 to 20.83%. Although it was not possible to draw a definite conclusion concerning hidrocystoma aetiopathogenesis, the relatively high Ki67-proliferative index observed, suggested a proliferative nature of the lesion. [Copyright &y& Elsevier]

Abstract: The present paper reveals the potential uses of novel hybrids of chitosan-g-lactic acid and sodium montmorillonite (MMT) in controlled drug delivery and tissue engineering applications. The drug-loaded novel nanohybrid films and porous scaffolds have been prepared by solvent casting and freeze-drying of the grafted polymer solution, respectively. Sodium Ibuprofen was loaded into nanohybrids of chitosan-g-lactic acid/sodium montmorillonite (CS-g-LA/MMT). Grafting of lactic acid and the drug loading were characterized by Fourier transform infrared spectroscopy. Formation of intercalated nanocomposites was confirmed by X-ray diffraction. Mechanical properties measurements have shown improvement in modulus and strength with expense of elongation by MMT reinforcement. The nanohybrids were found to be stable regardless of pH of the medium. The cell proliferation profile also shows that prepared nanohybrids are biocompatible. MMT reinforcement was found to control the drug (Ibuprofen) release rate in phosphate buffer saline solution (pH 7.4). MMT clay is therefore a viable additive for formulating sustained drug delivery systems based on lactic acid grafted chitosan. [Copyright &y& Elsevier]

Abstract: The central role of the cytoskeleton in both healthy and diseased cellular functions makes it a compelling subject for detailed three-dimensional (3D) micromechanical modeling. Microstructural features of the cytoskeleton govern the cell’s mechanical behavior in many of the regulating cellular functions including cell division, adhesion, spreading, migration, contraction, and other mechanotransductive effects which influence biochemical processes. Actin microfilaments (AF) combine to form one of the predominant cytoskeletal networks important to these biological processes. Here, the AF cytoskeletal microstructure and stress-strain behavior is modeled via a microstructurally-informed continuum mechanics approach. The force-extension behavior of the individual filaments is captured using the MacKintosh derivation of the worm-like chain (WLC) constitutive relationship for short chains where a new and direct analytical expression for the filament force as a function of filament extension is developed in this paper. The filament force-extension behavior is then used in conjunction with the Arruda-Boyce eight-chain network model to capture the 3D multiaxial stress-strain behavior of the network. The resulting 3D cytoskeletal network constitutive model provides the ability to track microstructural stretch and orientation states during 3D macroscopic stretching conditions. The non-affine nature of the network model effectively accommodates the imposed macroscopic shear strain through filament rotation and a relatively small amount of filament stretch. These characteristics enable the network model, using physically realistic material properties, to capture the initial stiffness of the AF network as well as the nonlinear strain stiffening observed at large stresses. The network model predictions compare favorably with published microrheological data of in vitro AF networks. [Copyright &y& Elsevier]

The following Accepted Article from FEBS Open Bio, 'MicroRNA-491 and microRNA-1306 target hTERT to inhibit proliferation and invasion in ovarian cancer cells' by Lin Bai, Hui Wang, Ai-Hua Wang, Luo-Ying Zhang and Jie Bai, published online on 10 November 2016 in Wiley Online Library (), has been retracted by agreement between the authors, the journal Executive Editor Mary Purton and John Wiley & Sons. The retraction has been agreed due to inconsistencies in the data for miR-1306 contained in this paper with recent results in other ovarian cancer cell lines as yet unpublished. This paper has been withdrawn until further confirmatory experiments are carried out. [ABSTRACT FROM AUTHOR]

Growing evidence shows that stem cells are modulated by systemic factors that are integrated with local signals in response to physiological status. Two recent Cell (Chell and Brand, 2010) and Nature (Sousa-Nunes et al., 2011) papers reveal that Drosophila neural stem cell proliferation is controlled by a diet-dependent insulin/TOR signaling relay between tissues. [ABSTRACT FROM AUTHOR]