Liver fibrosis pathologies and potentials of RNA based therapeutics modalities.

Liver fibrosis (LF) occurs when the liver tissue responds to injury or inflammation by producing excessive amounts of scar tissue, known as the extracellular matrix. This buildup stiffens the liver tissue, hinders blood flow, and ultimately impairs liver function. Various factors can trigger this process, including bloodborne pathogens, genetic predisposition, alcohol abuse, non-steroidal anti-inflammatory drugs, non-alcoholic steatohepatitis, and non-alcoholic fatty liver disease.

The beneficial role of exercise in preventing doxorubicin-induced cardiotoxicity.

Doxorubicin is a highly effective chemotherapeutic agent widely used to treat a variety of cancers. However, the clinical application of doxorubicin is limited due to its adverse effects on several tissues. One of the most serious side effects of doxorubicin is cardiotoxicity, which results in life-threatening heart damage, leading to reduced cancer treatment success and survival rate.

Implications of Neural Plasticity in Retinal Prosthesis.

Retinal degenerative diseases such as retinitis pigmentosa cause a progressive loss of photoreceptors that eventually prevents the affected person from perceiving visual sensations. The absence of a visual input produces a neural rewiring cascade that propagates along the visual system. This remodeling occurs first within the retina.

Adding Tree Rings to North America's National Forest Inventories: An Essential Tool to Guide Drawdown of Atmospheric CO2.

Tree-ring time series provide long-term, annually resolved information on the growth of trees. When sampled in a systematic context, tree-ring data can be scaled to estimate the forest carbon capture and storage of landscapes, biomes, and-ultimately-the globe. A systematic effort to sample tree rings in national forest inventories would yield unprecedented temporal and spatial resolution of forest carbon dynamics and help resolve key scientific uncertainties, which we highlight in terms of evidence for forest greening (enhanced growth) versus browning (reduced growth, increased mortality).

Interplay between cellular activity and three-dimensional scaffold-cell constructs with different foam structure processed by electron beam melting.

The cellular activity, biological response, and consequent integration of scaffold-cell construct in the physiological system are governed by the ability of cells to adhere, proliferate, and biomineralize. In this regard, we combine cellular biology and materials science and engineering to fundamentally elucidate the interplay between cellular activity and interconnected three-dimensional foamed architecture obtained by a novel process of electron beam melting and computational tools. Furthermore, the organization of key proteins, notably, actin, vinclulin, and fibronectin, involved in cellular activity and biological functions and relationship with the structure was explored.

Cholinergic and nitrergic neuronal networks in the goldfish telencephalon.

The general organization of cholinergic and nitrergic elements in the central nervous system seems to be highly conserved among vertebrates, with the involvement of these neurotransmitter systems now well established in sensory, motor and cognitive processing. The goldfish is a widely used animal model in neuroanatomical, neurophysiological, and behavioral research. The purpose of this study was to examine pallial and subpallial cholinoceptive, cholinergic and nitrergic populations in the goldfish telencephalon by means of histochemical and immunohistochemical techniques in order to identify neurons containing acetylcholinesterase (AChE), choline acetyltransferase (ChAT), NADPH-diaphorase (NADPHd), and neuronal nitric oxide synthase (nNOS), and to relate their distribution to their putative functional significance.

Interactions between postnatal sustained hypoxia and intermittent hypoxia in the adulthood to alter brainstem structures and respiratory function.

Neural plasticity is defined as a persistent change in the morphology and/or function based on prior experiences. Plasticity is well evident when the triggering experience occurs early in life, but in the case of respiratory control plasticity, it also can be triggered in adult life. We have combined a 10 days postnatal hypoxic (PH) (0-10 days of age;11% O(2)) and a 15 days intermittent hypoxia (IH) exposures in the adulthood (90-105 days of age; 5% O(2), 40 s/20% O(2), 80 s; 8 h/day) to test if early PH interacts with IH of the adulthood to generate detrimental plastic changes.

Next generation orthopaedic implants by additive manufacturing using electron beam melting.

This paper presents some examples of knee and hip implant components containing porous structures and fabricated in monolithic forms utilizing electron beam melting (EBM). In addition, utilizing stiffness or relative stiffness versus relative density design plots for open-cellular structures (mesh and foam components) of Ti-6Al-4V and Co-29Cr-6Mo alloy fabricated by EBM, it is demonstrated that stiffness-compatible implants can be fabricated for optimal stress shielding for bone regimes as well as bone cell ingrowth. Implications for the fabrication of patient-specific, monolithic, multifunctional orthopaedic implants using EBM are described along with microstructures and mechanical properties characteristic of both Ti-6Al-4V and Co-29Cr-6Mo alloy prototypes, including both solid and open-cellular prototypes manufactured by additive manufacturing (AM) using EBM.

Neonatal caffeine treatment up-regulates adenosine receptors in brainstem and hypothalamic cardio-respiratory related nuclei of rat pups.

While neonatal caffeine treatment is commonly used to alleviate apnea of prematurity in neonates and to improve neurological outcomes, its effects on adenosine A₁ and A(2A) receptors (A₁-R and A(2A)-R) are poorly known. We hypothesized that the central pharmacological action of caffeine is mediated by modification of the postnatal development of the adenosinergic system during a critical period. On postnatal days 2-6 (P2-P6) two groups of newborn rats were orally administered water plus glucose and/or caffeine at therapeutic doses to mimic the clinical use of caffeine in human neonates.

Evaluation of Titanium Alloys Fabricated Using Rapid Prototyping Technologies-Electron Beam Melting and Laser Beam Melting.

This study characterized properties of Ti-6Al-4V ELI (extra low interstitial, ASTM grade 23) specimens fabricated by a laser beam melting (LBM) and an electron beam melting (EBM) system for dental applications. Titanium alloy specimens were made into required size and shape for each standard test using fabrication methods. The LBM specimens were made by an LBM machine utilizing 20 µm of Ti-6Al-4V ELI powder.

Microstructure and mechanical properties of open-cellular biomaterials prototypes for total knee replacement implants fabricated by electron beam melting.

Total knee replacement implants consisting of a Co-29Cr-6Mo alloy femoral component and a Ti-6Al-4V tibial component are the basis for the additive manufacturing of novel solid, mesh, and foam monoliths using electron beam melting (EBM). Ti-6Al-4V solid prototype microstructures were primarily α-phase acicular platelets while the mesh and foam structures were characterized by α(')-martensite with some residual α. The Co-29Cr-6Mo containing 0.

Characterization and cytotoxic assessment of ballistic aerosol particulates for tungsten alloy penetrators into steel target plates.

The nature and constituents of ballistic aerosol created by kinetic energy penetrator rods of tungsten heavy alloys (W-Fe-Ni and W-Fe-Co) perforating steel target plates was characterized by scanning and transmission electron microscopy. These aerosol regimes, which can occur in closed, armored military vehicle penetration, are of concern for potential health effects, especially as a consequence of being inhaled. In a controlled volume containing 10 equispaced steel target plates, particulates were systematically collected onto special filters.

Evidence of low-temperature superparamagnetism in Mn3O4 nanoparticle ensembles.

Using ac-susceptibility, dc-magnetization, and transmission electron microscopy, we have investigated the magnetic behavior of Mn(3)O(4) nanoparticle ensembles at temperatures below the paramagnetic-to-ferrimagnetic transition of the title material (T(N) approximately equal 41 K). Our data show no evidence of the complex magnetic ordering exhibited by bulk Mn(3)O(4), or of a magnetic behavior around T(N) that has a dynamic (relaxation) origin. Instead, we find a low-temperature (at approximately 11 K) magnetic anomaly that manifests itself as a peak in the out-of-phase component of the ac-susceptibility.

Next-generation biomedical implants using additive manufacturing of complex, cellular and functional mesh arrays.

In this paper, we examine prospects for the manufacture of patient-specific biomedical implants replacing hard tissues (bone), particularly knee and hip stems and large bone (femoral) intramedullary rods, using additive manufacturing (AM) by electron beam melting (EBM). Of particular interest is the fabrication of complex functional (biocompatible) mesh arrays. Mesh elements or unit cells can be divided into different regions in order to use different cell designs in different areas of the component to produce various or continually varying (functionally graded) mesh densities.

Microstructure and mechanical behavior of Ti-6Al-4V produced by rapid-layer manufacturing, for biomedical applications.

The microstructure and mechanical behavior of simple product geometries produced by layered manufacturing using the electron beam melting (EBM) process and the selective laser melting (SLM) process are compared with those characteristic of conventional wrought and cast products of Ti-6Al-4V. Microstructures are characterized utilizing optical metallography (OM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and included alpha (hcp), beta (bcc) and alpha(') (hcp) martensite phase regimes which give rise to hardness variations ranging from HRC 37 to 57 and tensile strengths ranging from 0.9 to 1.

Co-localization of nitric oxide synthase and choline acetyltransferase in the brain of the goldfish (Carassius auratus).

This work investigates the nitrergic and cholinergic systems in the brain and spinal cord of the goldfish (Carassius auratus). We studied the immunohistochemical localization of antibodies against the neuronal nitric oxide synthase (nNOS) and choline acetyltransferase (ChAT) by bright-field and confocal microscopy. Nitrergic and cholinergic cells were segregated within the telencephalon, in both dorsal and ventral areas, and co-distributed in some nuclei of the diencephalon, mesencephalon, rhombencephalon, and spinal cord.

Prenatal activation of 5-HT2A receptor induces expression of 5-HT1B receptor in phrenic motoneurons and alters the organization of their premotor network in newborn mice.

In newborn mice of the control [C3H/HeJ (C3H)] and monoamine oxidase A-deficient (Tg8) strains, in which levels of endogenous serotonin (5-HT) were drastically increased, we investigated how 5-HT system dysregulation affected the maturation of phrenic motoneurons (PhMns), which innervate the diaphragm. First, using immunocytochemistry and confocal microscopy, we observed a 5-HT(2A) receptor (5-HT(2A)-R) expression in PhMns of both C3H and Tg8 neonates at the somatic and dendritic levels, whereas 5-HT(1B) receptor (5-HT(1B)-R) expression was observed only in Tg8 PhMns at the somatic level. We investigated the interactions between 5-HT(2A)-R and 5-HT(1B)-R during maturation by treating pregnant C3H mice with a 5-HT(2A)-R agonist (2,5-dimethoxy-4-iodoamphetamine hydrochloride).

Distribution of NADPH-diaphorase and nitric oxide synthase reactivity in the central nervous system of the goldfish (Carassius auratus).

The nitrergic system has been inferred from cells positive to nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry and/or to the neuronal isoform of nitric oxide synthase (nNOS) immunohistochemistry in different species of vertebrates. The aim of the present work was to systematically study the distribution of cell producing nitric oxide in the goldfish (Carassius auratus) brain. To reach this goal, we firstly studied co-localization for NADPHd and nNOS techniques and demonstrated an extensive double labeling.

Effect of postnatal exposure to caffeine on the pattern of adenosine A1 receptor distribution in respiration-related nuclei of the rat brainstem.

Caffeine, which belongs to the methylxantine family of compounds, is commonly ingested in a range of beverages such as coffee, tea, and cola drinks. It is also used therapeutically and is frequently employed in the treatment of respiratory disturbances in human neonates. The aim of the present work has been to examine the ontogeny of the adenosine A1 receptor system in the brainstem of the newborn rat following postnatal treatment with caffeine to mimic the therapeutic administration of caffeine to premature human infants.

An experimental approach to the fundamental principles of hemodynamics.

An experimental model has been developed to give students hands-on experience with the fundamental laws of hemodynamics. The proposed experimental setup is of simple construction but permits the precise measurements of physical variables involved in the experience. The model consists in a series of experiments where different basic phenomena are quantitatively investigated, such as the pressure drop in a long straight vessel and in an obstructed vessel, the transition from laminar to turbulent flow, the association of vessels in vascular networks, or the generation of a critical stenosis.

Characterization of efferent projections of chemosensitive neurons in the caudal parapyramidal area of the rat brain.

The caudal parapyramidal area of the rat brain contains a population of neurons that are highly sensitive to an increase in the extracellular hydrogen ion concentration ([H+]o). Some of them fire synchronously with respiration when [H+]o is increased. These chemosensitive neurons are located in the caudal ventrolateral medulla in a medial region, closest to the pyramidal tract, and a lateral region, beneath the lateral reticular nucleus.

Involvement of adenosinergic A1 systems in the occurrence of respiratory perturbations encountered in newborns following an in utero caffeine exposure. a study on brainstem-spinal cord preparations isolated from newborn rats.

Involvement of adenosinergic A1 systems in the occurrence of respiratory perturbations encountered in newborns following an in utero caffeine exposure has been investigated on pontomedullary-spinal cord, caudal pons-medullary-spinal cord and medullary-spinal cord preparations isolated from newborn rats. According to the drinking fluid of dams (tap water or 0.02% caffeine), two groups of preparations were distinguished, no-caffeine and caffeine.

Highly H+-sensitive neurons in the caudal ventrolateral medulla of the rat.

The ventral surface of the caudal ventrolateral medulla (cVLM) has been shown to generate intense respiratory responses after surface acid-base stimulation. With respect to their chemosensitive characteristics, cVLM neurons have been less studied than other rostral-most regions of the brainstem. The purpose of these experiments was to determine the bioelectric responses of cVLM neurons to acidic stimuli and to determine their chemosensitive properties.