Higher Fiber Density Research Articles

Immunohistochemical Study of the Goat Ductus deferens

Abstract Ductus deferens plays an important role in sperm transport and participates in the preservation of structure, maturation, and viability of sperm. In this study, we have immunohistochemically examined the ductus deferens in the goat. For immunohistochemical study the following monoclonal antibodies were used: cytokeratin 18, α-smooth muscle actin (α-SMA), vimentin and elastin. Morphologically, three distinct layers were identified in the goat ductus deferens — tunica mucosa, tunica muscularis and tunica adventitia. The epithelium of the mucosa was intensely stained with cytokeratin 18 (CK 18). The fibroblasts in the lamina propria and blood capillaries in the muscle layer showed positive reaction for vimentin. A positive reaction for α-SMA was observed in the smooth muscle cells of the tunica muscularis in the internal, middle and outer sublayers. An intense positive reaction for α-SMA was observed in the wall of the blood vessels. Elastic fibers in the form of a loose meshwork were present in all three layers. The high density of elastic fibers were found in the tunica adventitia.

Behavioral sensitization induced by dorsal periaqueductal gray electrical stimulation is counteracted by NK1 receptor antagonism in the ventral hippocampus and central nucleus of the amygdala.

A single threatening experience may change the behavior of an animal in a long-lasting way and elicit generalized behavioral responses to a novel threatening situation that is unrelated to the original aversive experience. Electrical stimulation (ES) of the dorsal periaqueductal gray (dPAG) produces a range of defensive reactions, characterized by freezing, escape, and post-stimulation freezing (PSF). The latter reflects the processing of ascending aversive information to prosencephalic structures, including the central nucleus of the amygdala (CeA), which allows the animal to evaluate the consequences of the aversive situation. This process is modulated by substance P (SP) and its preferred receptor, neurokinin 1 (NK1). The ventral hippocampus (VH) has been associated with the processing of aversive information and expression of emotional reactions with negative valence, but the participation of the VH in the expression of these defensive responses has not been investigated. The VH is rich in NK1 receptor expression and has a high density of SP-containing fibers. The present study examined the role of NK1 receptors in the VH in the expression of defensive responses and behavioral sensitization that were induced by dPAG-ES. Rats were implanted with an electrode in the dPAG for ES, and a cannula was implanted in the VH or CeA for injections of vehicle (phosphate-buffered saline) or the NK1 receptor antagonist spantide (100 pmol/0.2 μL. Spantide reduced the duration of PSF that was evoked by dPAG-ES, without changing the aversive freezing or escape thresholds. One and 7 days later, exploratory behavior was evaluated in independent groups of rats in the elevated plus maze (EPM). dPAG-ES in rats that received vehicle caused higher aversion to the open arms of the EPM compared with rats that did not receive dPAG stimulation at both time intervals. Injections of spantide in the VH or CeA prevented the proaversive effects of dPAG-ES in the EPM only 1 day later. These findings suggest that NK1 receptors are activated in both the VH and CeA during the processing of aversive information that derives from dPAG-ES. As previously shown for the CeA, SP/NK1 receptors in the VH are recruited during PSF that is evoked by dPAG-ES, suggesting that a 24-h time window is susceptible to interventions with NK1 antagonists that block the passage of aversive information from the dPAG to higher brain areas.

Registration of ‘UA107’ Okra‐Leaf Cotton Cultivar

‘UA107’ (Reg. No. CV‐136, PI 685638) is a conventional open‐canopy cultivar of cotton (Gossypium hirsutum L.) released by the Arkansas Agricultural Experiment Station in February 2017. The cultivar was released as part of an ongoing effort to develop improved genotypes having enhanced yield, yield components, earliness, host plant resistance, and fiber properties. UA107 expressed earlier maturation than ‘DP 393’, which is considered a short‐season cultivar. When evaluated over years and locations in Arkansas, lint yields of UA107 were higher than DP 393 and ‘UA48’ except at Keiser, where its yields were equal to DP 393. Lint yields of UA107 were associated with greater lint index, more fibers per seed, fewer seed produced per area, and higher fiber density. Across the 12 locations of the 2015 Regional Breeders’ Testing Network, UA107 produced the second‐highest lint yield of 28 entries, which suggests that it is widely adapted. UA107 displays high resistance to bacterial blight and Fusarium wilt but is more sensitive than DP 393 to tarnished plant bugs. UA107 exhibited longer fiber length and lower micronaire than DP 393. These fiber qualities are positively related to better spinning performance. UA107 displays an unusual combination of high yielding ability, very early maturity, high fiber quality, and host plant resistance traits. UA107 is a very early maturing, widely adapted, conventional cultivar that produces good fiber quality.

Correction of GSK3β at young age prevents muscle pathology in mice with myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a progressive neuromuscular disease caused by expanded CUG repeats, which misregulate RNA metabolism through several RNA-binding proteins, including CUG-binding protein/CUGBP1 elav-like factor 1 (CUGBP1/CELF1) and muscleblind 1 protein. Mutant CUG repeats elevate CUGBP1 and alter CUGBP1 activity via a glycogen synthase kinase 3β (GSK3β)-cyclin D3-cyclin D-dependent kinase 4 (CDK4) signaling pathway. Inhibition of GSK3β corrects abnormal activity of CUGBP1 in DM1 mice [human skeletal actin mRNA, containing long repeats ( HSALR) model]. Here, we show that the inhibition of GSK3β in young HSALR mice prevents development of DM1 muscle pathology. Skeletal muscle in 1-yr-old HSALR mice, treated at 1.5 mo for 6 wk with the inhibitors of GSK3, exhibits high fiber density, corrected atrophy, normal fiber size, with reduced central nuclei and normalized grip strength. Because CUG-GSK3β-cyclin D3-CDK4 converts the active form of CUGBP1 into a form of translational repressor, we examined the contribution of CUGBP1 in myogenesis using Celf1 knockout mice. We found that a loss of CUGBP1 disrupts myogenesis, affecting genes that regulate differentiation and the extracellular matrix. Proteins of those pathways are also misregulated in young HSALR mice and in muscle biopsies of patients with congenital DM1. These findings suggest that the correction of GSK3β-CUGBP1 pathway in young HSALR mice might have a positive effect on the myogenesis over time.-Wei, C., Stock, L., Valanejad, L., Zalewski, Z. A., Karns, R., Puymirat, J., Nelson, D., Witte, D., Woodgett, J., Timchenko, N. A., Timchenko, L. Correction of GSK3β at young age prevents muscle pathology in mice with myotonic dystrophy type 1.

Investigation of Conical Spinneret in Generating More Dense and Compact Electrospun Nanofibers.

Electrospinning is an important, widely used process to generate nanofibers. However, there is still an open window for different designs of both spinneret and collector electrodes to be investigated. This paper introduces the impact of new design of conical spinneret electrode on the generated electrospun nanofibers. In this work, the conical feeder is used to generate electrospun Poly(vinyl alcohol) (PVA) nanofibers, and being compared to the traditional needle feeder at the same processing conditions. The jet’s mechanism is simulated using discrete bead model along with estimated calculations of both deposition area and fiber radius. The electric field distribution that is around the charged cone is analyzed. Based on both theoretical modeling and experimental measurements, a comparison of mean diameter, deposited area, and the thickness of generated nanofibers is presented related to both conical and needle electrodes. Conical feeder shows clearly compact nanofibers mat in terms of deposition area (spherical deposition of diameter ~6 cm) up to half-area of needle deposited nanofibers with high fiber density for the same time of the process. Moreover, the conical electrode is found to have privilege in terms of productivity rate and operation time. This study can be useful in generating localized nanofibers within different applications, such as biomedical tissue scaffolds, textile, and sensors.

Role of ITO nanoparticles embedded into electrospun ITO nanofibers

Both crystallization and molecular density are significant to achieve high electrical conductivity of transparent electrodes. Herein, we investigated the embedding effects of indium tin oxide (ITO) nanoparticles (NPs) into ITO nanofibers (NFs) synthesized by utilizing an electrospinning technique from ITO precursor solutions. We found that the ITO NPs might act as nucleation seeds that initiate crystallization of ITO, evidenced by flake-like morphologies which cannot be observed without ITO NPs. XRD measurements reveal that the ITO is crystalline with a higher degree and the size of ITO crystallites increases in the presence of ITO NPs embedded into NFs. Embedding ITO NPs leads to the formation of short fibers, but there is still large space between fibers as they are vertically stacked in the films, resulting in low electrical conductivity. Interestingly, a high ratio of ITO NPs enhances the electrical conductivity, as compared to a low ratio, which we attribute to the high fiber density on substrates due to the formation of shorter ITO NFs. Our results highlight that the ITO NPs influence not only the ITO crystallization but also the lengths of NFs. High electrical conductivity of NF films can be obtained by a high degree of crystallization and the optimum NF length that reduces spaces between NFs in the films.

Novel bioresorbable phosphate glass fiber textile composites for medical applications

A manual bench‐top Inkle‐type loom was designed to enable hand woven textiles. These phosphate glass fiber (PGF) textiles, along with unidirectional (UD) fiber mats made from the same batch of yarns, were utilized to manufacture fully resorbable textile composites (T‐C), unidirectional aligned fiber composites (UD‐C), and 0°/90° lay‐up UD fiber‐reinforced composites (0/90‐C). The fiber volume fraction in the composites was set at ∼20%. Retention of flexural properties and mass loss of the composites were evaluated during degradation in phosphate buffered saline (PBS) at 37°C for 28 days. The higher flexural strength and modulus values observed for the T‐C when compared to 0/90‐C were attributed to the textile weaving resulting in a biased fabric with a higher density of fibers in the warp direction. After 28 days immersion in PBS, ∼20% flexural strength and ∼25% flexural modulus values for the UD‐C, T‐C, and 0/90‐C composites were still prevalent. POLYM. COMPOS., 39:E140–E151, 2018. © 2017 Society of Plastics Engineers

Design and fabrication of porous chitosan scaffolds with tunable structures and mechanical properties

Chitosan-based porous scaffolds are of great interest in biomedical applications because of their biodegradability and biocompatibility. However, the poor mechanical properties of these scaffolds hinder their broad utility. In the present study, a novel compression method was developed to fabricate chitosan scaffolds with high mechanical strength and tuneable topography, based on the ionic strength and pH-dependent solubility of chitosan. When the compressive ratio increases from 1 to 8, the compressive elastic modulus of the scaffold increases from 5.2kPa to 520kPa and the porosity decreases from 94.1% to 82.5%. Furthermore, the number of human adipose-derived stem cells adhering to the scaffolds increases as the compressive ratio increases, owing to the high density of the chitosan fibres. This method does not require external cross-linker agent, sophisticated instrumentation and/or technical proficiency and could be extended to other polysaccharides.

Composition and structure of porcine digital flexor tendon-bone insertion tissues.

Tendon-bone insertion is a functionally graded tissue, transitioning from 200 MPa tensile modulus at the tendon end to 20 GPa tensile modulus at the bone, across just a few hundred micrometers. In this study, we examine the porcine digital flexor tendon insertion tissue to provide a quantitative description of its collagen orientation and mineral concentration by using Fast Fourier Transform (FFT) based image analysis and mass spectrometry, respectively. Histological results revealed uniformity in global collagen orientation at all depths, indicative of mechanical anisotropy, although at mid-depth, the highest fiber density, least amount of dispersion, and least cellular circularity were evident. Collagen orientation distribution obtained through 2D FFT of histological imaging data from fluorescent microscopy agreed with past measurements based on polarized light microscopy. Results revealed global fiber orientation across the tendon-bone insertion to be preserved along direction of physiologic tension. Gradation in the fiber distribution orientation index across the insertion was reflective of a decrease in anisotropy from the tendon to the bone. We provided elemental maps across the fibrocartilage for its organic and inorganic constituents through time-of-flight secondary ion mass spectrometry (TOF-SIMS). The apatite intensity distribution from the tendon to bone was shown to follow a linear trend, supporting past results based on Raman microprobe analysis. The merit of this study lies in the image-based simplified approach to fiber distribution quantification and in the high spatial resolution of the compositional analysis. In conjunction with the mechanical properties of the insertion tissue, fiber, and mineral distribution results for the insertion from this may potentially be incorporated into the development of a structural constitutive approach toward computational modeling. Characterizing the properties of the native insertion tissue would provide the microstructural basis for developing biomimetic scaffolds to recreate the graded morphology of a fibrocartilaginous insertion. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3050-3058, 2017.

Analysis of DNA Replication in Fission Yeast by Combing.

DNA replication studies based on population experiments give an average estimate of replication kinetics from many cells. This average replication profile masks the stochastic nature of origin firing in eukaryotes, which is revealed by using single-molecule techniques, such as DNA combing. The analysis of replication kinetics by DNA combing involves isolating DNA from cells that have been pulse-labeled with thymidine analogs and stretching it on a silanized coverslip. The analog-labeled patches on the stretched DNA fibers can then be detected using fluorescent antibodies against the analog. Each fiber represents a part of the genome from a single cell; therefore, it is possible to study the variation in behavior of individual origins from one cell to another. Furthermore, each DNA fiber is uniformly stretched, making it possible to measure distances accurately at kilobase resolution. It is also possible to stretch a high density of fibers on coverslips enabling quantitative data collection.

Collagen Fiber Architecture Regulates Hypoxic Sarcoma Cell Migration.

Collagen is prevalent in the microenvironment of many cancer types and has been demonstrated to play an important role during disease progression. We previously showed the importance of hypoxic gradients in sarcoma cell migration. Here, we utilized an oxygen gradient collagen gel platform to determine the impact of collagen fiber density and hypoxic gradient on sarcoma cell migration. The oxygen gradient was created by regulating the oxygen diffusion coefficient along with the cellular oxygen consumption rate. Collagen fiber density in the hydrogels is modified by changing the preincubation period of the collagen gel solution at 4 °C, controlling fiber density independently of collagen concentration and oxygen tension. High fiber density gels have wider and longer fibers but a similar microscale pore size with a larger nanoscale pore size and quicker stress relaxation time, compared to the low fiber density gel. Both gels have the same Young's modulus. We analyzed responses of sarcoma cells encapsulated in the different hydrogels for 3 days. In the nonhypoxic low fiber density constructs, sarcoma cells exhibit a larger aspect ratio, and the matrix has less fiber alignment compared to the nonhypoxic high fiber density constructs. Interestingly, we found a minimal effect of fiber density on cell migration and the ability of the cells to degrade the matrix in nonhypoxic constructs. When compared with hypoxic constructs, we observed the opposite trend, where cells in low fiber density constructs exhibit a lower aspect ratio and the matrix has more aligned fibers compared to hypoxic high fiber density constructs. Sarcoma cells encapsulated in high fiber density hypoxic gels migrated faster and degraded the matrix more rapidly compared to the low fiber density hypoxic constructs. Overall, we show that hypoxic cell migration and matrix degradation are enhanced in high fiber density gels, while hypoxic matrix alignment is prominent in low fiber density gels. Our results suggest that the differences in cellular responses under hypoxic gradients are due to the hydrogel architecture including fiber density, size (length and width), and stress relaxation.

Hybridisation of two ductile materials – Steel fibre and self-reinforced polypropylene composites

Hybridisation of self-reinforced polypropylene (SRPP) with ductile steel fibres is proposed as a way to create composites with a high stiffness, failure strain and toughness. The stiffness and yield stress of SRPP were significantly increased without sacrifice of toughness, even after normalisation to the composite density. The measurements revealed a higher stress level and slope after yielding than the predictions by the linear rule-of-mixtures. This effect was attributed to differences in the Poisson contraction of the two constituents and was supported by modelling predictions. The absolute penetration impact resistance of SRPP was increased, whereas the specific impact resistance remained the same, despite the high density of steel fibres. Placing steel fibre layers on the outside of the laminate maximised the penetration impact resistance, as it allowed the steel fibres to exploit their full plastic potential. These results can guide the optimisation of other hybrid composites with two ductile fibres.

MICROCOSM EXPERIMENTS ON A COCONUT-FIBRE BIOFILM TREATMENT SYSTEM TO EVALUATE WASTE WATER TREATMENT EFFICIENCIES

Interest in utilization of locally available biomasses as biofilm support media for wastewatertreatment in developing countries is increasing. In this study, microcosm experiments on a coconut-fibrebiofilm treatment system were carried out to evaluate wastewater treatment efficiencies in the laboratory usingtwo wastewaters, synthetic sewage and leachate, with different pollutant loads. Three coconut-fibre conditionswere set as a single bundle (low fibre density: LFD), two bundles (high fibre density: HFD), and no coconutfibre (blank). The wastewater was first circulated in the system for six weeks (circulation stage) and thendischarged from the treatment tank for 7–24 weeks (treatment stage). Water quality parameters of effluents,pH, DO, EC, BOD, COD, TC, and TN, were measured at one-week intervals, and the sedimented sludge ineach treatment tank was collected to determine C, N, and P contents. Results showed effective reductions inBOD and COD in the LFD and HFD conditions for the synthetic leachate, indicating that the coconut fibrecontributed to the treatment of wastewater. On the other hand, the fibre density had less or no effect on thereduction of water quality parameters in the synthetic sewage. For both synthetic sewage and leachate, the Cand N consumptions generally increased in the order of blank, LFD, and HFD. In particular, sludgesedimentation contributed to C consumption under the HFD condition.

Serotonin Regulates the Firing of Principal Cells of the Subiculum by Inhibiting a T-type Ca2+ Current.

The subiculum is the main output of the hippocampal formation. A high proportion of its principal neurons fire action potentials in bursts triggered by the activation of low threshold calcium currents. This firing pattern promotes synaptic release and regulates spike-timing-dependent plasticity. The subiculum receives a high density of fibers originating from the raphe nuclei, suggesting that serotonin (5-HT) modulates subicular neurons. Here we investigated if and how 5-HT modulates the firing pattern of bursting neurons. By combining electrophysiological analysis with pharmacology, optogenetics and calcium imaging, we demonstrate that 5-HT2C receptors reduce bursting activity by inhibiting a low-threshold calcium current mediated by T-type Ca2+ channels in principal cells of the subiculum. In addition, we show that the activation of this novel pathway decreases bursting activity and the occurrence of epileptiform discharges induced in in vitro models for temporal lobe epilepsy (TLE).

Growth induced buckling instability of anisotropic tube and its application in wound edge instability

Abstract Fiber reinforced anisotropic material abounds in biological world. It has been demonstrated in previous theoretical and experimental works that growth of biological soft tubular tissue plays a significant role in morphogenesis and pathology. Here we investigate growth-induced buckling of anisotropic cylindrical tissue, focusing on the effects of type of growth(constraint/unconstraint, isotropic/anisotropic), fiber property(orientation, density and strength), geometry and any interaction between these factors. We studied one-layer and two-layer models and obtained a rich spectrum of results. For one-layer model, we demonstrate that circumferential fiber orientation has a consistent stabilizing effect under various scenarios of growth. Higher fiber density has a destabilizing effect by disabling high-mode buckling. For two-layer model, we found that critical buckling strain at inner boundary is an invariant under same isotropic growth rate ratio between inner/ outer layer(g1 /g0). Then we applied our model to wound healing and illustrate the effects of skin residual stress, fiber property, proliferation region width and wound size on the wound edge stability. We conclude that fiber-reinforcement is an important factor to consider when investigating growth induced instability of anisotropic soft tissue.

Classification of Lacrimal Punctal Stenosis and Its Related Histopathological Feature in Patients with Epiphora.

PurposeTo evaluate the classification of punctal stenosis based on the shape of the external punctum, clinical characteristics and histopathologic features.MethodsPatients who experienced tearing and were diagnosed with punctal stenosis were evaluated in this study. Punctal stenosis was classified according to the shape of the lower external punctum, which included membranous type, slit type, horseshoe type, and pinpoint type. Tear meniscus height, 2% fluorescein dye disappearance test and lacrimal pathway irrigation were measured or performed. For treatment, a punctal snip operation and silicone tube placement were performed, and the peripunctal histopathological findings were evaluated.ResultsPunctal stenosis was classified into four types: membranous type (17 eyes, 21.5%), slit type (11 eyes, 13.9%), horseshoe type (25 eyes, 31.6%), and pinpoint type (26 eyes, 32.9%). The tear meniscus was significantly higher, and the 2% fluorescein dye disappeared significantly more slowly in the punctal stenosis group. However, correlation of the tear meniscus height and 2% fluorescein dye disappearance test with the punctum shape was not statistically significant. A history of previous chemotherapy was significantly associated with the occurrence of punctal stenosis, especially the membranous type (p < 0.05). Histopathologic evaluation of the punctum showed differences between the punctum types. Pinpoint puncta exhibited a high density of muscle fibers, while they were faintly visible in the membranous type.ConclusionsAcquired punctal stenosis has various shapes, and the major types of stenotic puncta exhibited unique histopathologic features. Punctal stenosis and its pathophysiology may be related to multiple factors, such as age and systemic 5-fluorouracil chemotherapy history.

Comparison of Characteristics of Myosin Heavy Chain-based Fiber and Meat Quality among Four Bovine Skeletal Muscles.

Muscle fiber characteristics account for meat quality and muscle fibers are mainly classified into three or more types according to their contractile and metabolic properties. However, the majority of previous studies on bovine skeletal muscle are based on myosin ATPase activity. In the present study, the differences in the characteristics of muscle fibers classified by the expression of myosin heavy chain (MHC) among four bovine skeletal muscles such as longissimus thoracis (LT), psoas major (PM), semimembranosus (SM) and semitendinosus (ST) and their relationships to beef quality were investigated. MHCs 2x, 2a and slow were identified by LC-MS/MS and IIX, IIA and I fiber types were classified. PM, which had the smallest size and highest density of fibers regardless of type, showed the highest myoglobin content, CIE L*, a*, b* and sarcomere length (p<0.05), whereas ST with the highest composition of IIX, showed high shear force and low sarcomere length (p<0.05). The correlation coefficients between muscle fiber characteristics and meat quality showed that type IIX is closely related to poor beef quality and that a high density of small-sized fibers is related to redness and tenderness. Therefore, the differences in meat quality between muscles can be explained by the differences in muscle fiber characteristics, and especially, the muscles with good quality are composed of more small-sized fibers regardless of fiber type.

Thermal implications of interactions between insulation, solar reflectance, and fur structure in the summer coats of diverse species of kangaroo

Not all of thesolar radiation that impinges on a mammalian coat is absorbed and converted into thermal energy at the coat surface. Some is reflected back to the environment, while another portion is reflected further into the coat where it is absorbed and manifested as heat at differing levels. Substantial insulation in a coat limits the thermal impact at the skin of solar radiation, irrespective where in the coat it is absorbed. In coats with low insulation, the zone where solar radiation is absorbed may govern the consequent heat load on the skin (HL-SR). Thin summer furs of four species of kangaroo from differing climatic zones were used to determine how variation in insulation and in coat spectral and structural characteristics influence the HL-SR. Coat depth, structure, and solar reflectance varied between body regions, as well as between species. The modulation of solar radiation and resultant heat flows in these coats were measured at low (1ms-1) and high (6ms-1) wind speeds by mounting them on a heat flux transducer/temperature-controlled plate apparatus in a wind tunnel. A lamp with a spectrum similar to solar radiation was used as a proxy for the sun. We established that coat insulation was largely determined by coat depth at natural fur lie, despite large variations in fibre density, fibre diameter, and fur mass. Higher wind speed decreased coat insulation, but depth still determined the overall level. A multiple regression analysis that included coat depth (insulation), fibre diameter, fibre density, and solar reflectance was used to determine the best predictors of HL-SR. Only depth and reflectance had significant impacts and both factors had negative weights, so, as either insulation or reflectance increased, HL-SR declined, the larger impact coming from coat reflectance. This reverses the pattern observed in deep coats where insulation dominates over effects of reflectance. Across all coats, as insulation declined, reflectance increased. An increase in reflectance in the thinnest coats was not the sole reason for the limited rise in HL-SR. Higher reflectance should increase the depth of penetrance of solar radiation, thus increasing HL-SR. But in M. antilopinus and Macropus rufus, which had the highest of coat reflectances, penetrance was relatively shallow. This effect appears due to high fibre density (M. rufus) and major modifications in the fibre structure (M. antilopinus). The differing adaptations likely relate to the habitats of these species, desert in the case of M. rufus and monsoon tropical woodland with M. antilopinus.

Sympathetic nervous system promotes hepatocarcinogenesis by modulating inflammation through activation of alpha1-adrenergic receptors of Kupffer cells

The sympathetic nervous system (SNS) is known to play a significant role in tumor initiation and metastasis. Hepatocellular carcinoma (HCC) frequently occurs in cirrhotic livers after chronic inflammation, and the SNS is hyperactive in advanced liver cirrhosis. However, it remains unclear whether the SNS promotes hepatocarcinogenesis by modulating chronic liver inflammation. In this study, a retrospective pathological analysis and quantification of sympathetic nerve fiber densities (tyrosine hydroxylase, TH+) in HCC patients, and diethylnitrosamine (DEN)-induced hepatocarcinogenesis in rats were performed. Our data showed that high density of sympathetic nerve fibers and α1-adrenergic receptors (ARs) of Kupffer cells (KCs) were associated with a poor prognosis of HCC. Sympathetic denervation or blocking of α1-ARs decreased DEN-induced HCC incidence and tumor development. In addition, synergistic effects of interleukin-6 (IL-6) and transforming growth factor-beta (TGF-β) in hepatocarcinogenesis were observed. The suppression of the SNS reduced IL-6 and TGF-β expression, which suppressed hepatocarcinogenesis, and KCs play a key role in this process. After the ablation of KCs, IL-6 and TGF-β expression and the development of HCC were inhibited. This study demonstrates that sympathetic innervation is crucial for hepatocarcinogenesis and that the SNS promotes hepatocarcinogenesis by activating α1-ARs of KCs to boost the activation of KCs and to maintain the inflammatory microenvironment. These results indicate that sympathetic denervation or α1-ARs blockage may represent novel treatment approaches for HCC.

Atherosclerosis in the circle of Willis: Spatial differences in composition and in distribution of plaques

Background and aimsIntracranial atherosclerosis is one of the main causes of ischemic stroke. However, the characteristics of intracranial arteries and atherosclerosis have rarely been studied. Therefore, we systematically investigated atherosclerotic changes in all arteries of the Circle of Willis (CoW). MethodsSixty-seven CoWs obtained at autopsy from randomly chosen hospital patients (mean age, 67.3 ± 12.5 years), of which a total of 1220 segments were collected from 22 sites. Atherosclerotic plaques were classified according to the revised American Heart Association classification and were related to local vessel characteristics, such as the presence of an external and internal elastic lamina and the elastic fibre density of the media. Results181 out of the 1220 segments had advanced plaques (15%), which were mainly observed in large arteries such as the internal carotid, middle cerebral, basilar and vertebral artery. Only 11 out of 1220 segments (1%) showed complicated plaques (p < 0.001). Six of these were intraplaque hemorrhages (IPH) and observed only in patients who had cardiovascular-related events (p = 0.015). The frequency of characteristics such as the external elastic lamina and a high elastin fibre density in the media was most often associated with the vertebral artery. Only 3% (n = 33) of the CoW arteries contained calcification (p < 0.001), which were mostly observed in the vertebral artery (n = 13, 12%). ConclusionsAdvanced atherosclerotic plaques in the CoW are relatively scarce and mainly located in the 4 large arteries, and mostly characterized by an early and stable phenotype, a low calcific burden, and a low frequency of IPH.