Effects of hyperbaric oxygen on the osteogenic differentiation of mesenchymal stem cells

BACKGROUND: Hyperbaric oxygenation was shown to increase bone healing in a rabbit model. However, little is known about the regulatory factors and molecular mechanism involved.We hypothesized that the effect of hyperbaric oxygen (HBO) on bone formation is mediated via increases in the osteogenic differentiation of mesenchymal stem cells (MSCs) which are regulated by Wnt signaling. METHODS: The phenotypic characterization of the MSCs was analyzed by flow cytometric analysis. To investigate the effects of HBO on Wnt signaling and osteogenic differentiation of MSCs, mRNA and protein levels of Wnt3a, beta-catenin, GSK-3beta, Runx 2, as well as alkaline phosphatase activity, calcium deposition, and the intensity of von Kossa staining were analyzed after HBO treatment. To investigate the effects of HBO on Wnt processing and secretion, the expression of Wntless and vacuolar ATPases were quantified after HBO treatment. RESULTS: Cells expressed MSC markers such as CD105, CD146, and STRO-1. The mRNA and protein levels of Wnt3a, β-catenin, and Runx 2 were up-regulated, while GSK-3β was down-regulated after HBO treatment. Western blot analysis showed an increased β-catenin translocation with a subsequent stimulation of the expression of target genes after HBO treatment. The above observation was confirmed by small interfering (si)RNA treatment. HBO significantly increased alkaline phosphatase activity, calcium deposition, and the intensity of von Kossa staining of osteogenically differentiated MSCs. We further showed that HBO treatment increased the expression of Wntless, a retromer trafficking protein, and vacuolar ATPases to stimulate Wnt processing and secretion, and the effect was confirmed by siRNA treatment. CONCLUSIONS: HBO treatment increased osteogenic differentiation of MSCs via regulating Wnt processing, secretion, and signaling

Soft Phonon Mode Triggering Fast Ag Diffusion in Superionic Argyrodite Ag8_8GeSe6_6

The structural coexistence of dual rigid and mobile sublattices in superionic Argyrodites yields ultralow lattice thermal conductivity along with decent electrical and ionic conductivities and therefore attracts intense interest for batteries, fuel cells, and thermoelectric applications. However, a comprehensive understanding of their underlying lattice and diffusive dynamics in terms of the interplay between phonons and mobile ions is missing. Herein, inelastic neutron scattering is employed to unravel that phonon softening on heating to T$_c$ ≈ 350 K triggers fast Ag diffusion in the canonical superionic Argyrodite Ag$_8$GeSe$_6$. Ab initio molecular dynamics simulations reproduce the experimental neutron scattering signals and identify the partially ultrafast Ag diffusion with a large diffusion coefficient of 10$^{−4}$ cm$^{−2}$ s$^{−1}$. The study illustrates the microscopic interconnection between soft phonons and mobile ions and provides a paradigm for an intertwined interaction of the lattice and diffusive dynamics in superionic materials

Amorphous-Like Ultralow Thermal Transport in Crystalline Argyrodite Cu7PS6

Due to their amorphous-like ultralow lattice thermal conductivity both below and above the superionic phase transition, crystalline Cu- and Ag-based superionic argyrodites have garnered widespread attention as promising thermoelectric materials. However, despite their intriguing properties, quantifying their lattice thermal conductivities and a comprehensive understanding of the microscopic dynamics that drive these extraordinary properties are still lacking. Here, an integrated experimental and theoretical approach is adopted to reveal the presence of Cu-dominated low-energy optical phonons in the Cu-based argyrodite Cu7PS6. These phonons yield strong acoustic-optical phonon scattering through avoided crossing, enabling ultralow lattice thermal conductivity. The Unified Theory of thermal transport is employed to analyze heat conduction and successfully reproduce the experimental amorphous-like ultralow lattice thermal conductivities, ranging from 0.43 to 0.58 W m−1 K−1, in the temperature range of 100–400 K. The study reveals that the amorphous-like ultralow thermal conductivity of Cu7PS6 stems from a significantly dominant wave-like conduction mechanism. Moreover, the simulations elucidate the wave-like thermal transport mainly results from the contribution of Cu-associated low-energy overlapping optical phonons. This study highlights the crucial role of low-energy and overlapping optical modes in facilitating amorphous-like ultralow thermal transport, providing a thorough understanding of the underlying complex dynamics of argyrodites

Molecular serotyping of Haemophilus parasuis isolated from diseased pigs and the relationship between serovars and pathological patterns in Taiwan

Background Haemophilus parasuis is the etiological agent of Glässer’s disease, and causes severe economic losses in the swine industry. Serovar classification is intended as an indicator of virulence and pathotype and is also crucial for vaccination programs and vaccine development. According to a polysaccharide biosynthesis locus analysis, H. parasuis isolates could be classified by a molecular serotyping assay except serovars 5 and 12 detected by the same primer pair. The aim of this study was to identify H. parasuis isolates from diseased pigs in Taiwan by using a molecular serotyping assay and to analyze the relationship between serovars and pathological patterns. Methods From August 2013 to February 2017, a total of 133 isolates from 277 lesions on 155 diseased animals from 124 infected herds serotyped by multiplex PCR and analyzed with pathological data. Results The dominant serovars of H. parasuis in Taiwan were serovars 5/12 (37.6%), 4 (27.8%) and 13 (15%) followed by molecular serotyping non-typable (MSNT) isolates (13.5%). Nevertheless, the serovar-specific amplicons were not precisely the same sizes as previously indicated in the original publication, and MSNT isolates appeared with unexpected amplicons or lacked serovar-specific amplicons. Most H. parasuis isolates were isolated from nursery pigs infected with porcine reproductive and respiratory syndrome virus. The percentage of lung lesions (30.4%) showing H. parasuis infection was significantly higher than that of serosal lesions. Discussion Collectively, the distribution of serovars in Taiwan is similar to that found in other countries, but MSNT isolates remain due to genetic variations. Furthermore, pulmonary lesions may be optimum sites for H. parasuis isolation, the diagnosis of Glässer’s disease, and may also serve as points of origin for systemic H. parasuis infections in hosts

When Cytokinin, a Plant Hormone, Meets the Adenosine A2A Receptor: A Novel Neuroprotectant and Lead for Treating Neurodegenerative Disorders?

It is well known that cytokinins are a class of phytohormones that promote cell division in plant roots and shoots. However, their targets, biological functions, and implications in mammalian systems have rarely been examined. In this study, we show that one cytokinin, zeatin riboside, can prevent pheochromocytoma (PC12) cells from serum deprivation-induced apoptosis by acting on the adenosine A2A receptor (A2A-R), which was blocked by an A2A-R antagonist and a protein kinase A (PKA) inhibitor, demonstrating the functional ability of zeatin riboside by mediating through A2A-R signaling event. Since the A2A-R was implicated as a therapeutic target in treating Huntington’s disease (HD), a cellular model of HD was applied by transfecting mutant huntingtin in PC12 cells. By using filter retardation assay and confocal microscopy we found that zeatin riboside reversed mutant huntingtin (Htt)-induced protein aggregations and proteasome deactivation through A2A-R signaling. PKA inhibitor blocked zeatin riboside-induced suppression of mutant Htt aggregations. In addition, PKA activated proteasome activity and reduced mutant Htt protein aggregations. However, a proteasome inhibitor blocked both zeatin riboside-and PKA activator-mediated suppression of mutant Htt aggregations, confirming mediation of the A2A-R/PKA/proteasome pathway. Taken together, zeatin riboside might have therapeutic potential as a novel neuroprotectant and a lead for treating neurodegenerative disorders

Brainstem Excitability is Increased in Subjects with Palmomental Reflex

The palmomental reflex (PMR) is a brief contraction of the mentalis muscles caused by a scratch over the thenar eminence, i.e. a brainstem reflex to afferents of upper limb. Using electrophysio-logic methods, we studied the characteristics of brainstem excitability in PMR subjects. Methods: Ten healthy PMR subjects were included in the study. Brainstem excitability was assessed with electrical stimulation at the trigeminal nerve, median nerve, ulnar nerve, and sural nerve with recordings at the mentalis muscles. A comparison was made by the probability between the mechanical scratch and the electrical stimulation to evoke the visible muscle contraction of mentalis. Results: An electrical stimulus was able to elicit mentalis muscle responses (MMRelectrical) in all the subjects if the stimulus was of sufficient strength. Using electrical stimulation, the median nerve at the wrist was the best site to evoke MMRelectrical. However, in PMR subjects, the probability of MMRelectrical to median nerve stimulation was less than that of MMRscratch, i.e. the clinical findings of PMR. Significantly lower thresholds and higher amplitudes were noted in PMR subjects only when the median nerve was stimulated. The onset latency did not show any difference between the two groups despite the stimulation sites. Conclusion: The facial motor neurons to median nerve stimulation are more sensitive in PMR subjects. In healthy PMR subjects, this indicates that the excitability increases only in the specific neuronal circuits between the lower cervical spinal cord and the facial motor nucleus in the rostral medulla. MMRelectrical is a physiologic phenomenon, and PMR is a sign of increased brainstem excitability

Preserved motor-evoked potentials but without good motor recovery in a patient with decerebrate rigidity

The corticospinal tract is not incriminated in decerebrate rigidity (DR). However, this has not yet been proven in humans. We applied transcranial magnetic stimulation (TMS) in a decerebrate patient to support the hypothesis. A patient suffering from pontine hemorrhage with the fourth ventricular extension was admitted unconscious and in a decerebrate posture. Five days later, she regained consciousness but remained in a decerebrate posture. Motor-evoked potentials (MEPs) to TMS were measured 1 week after she had regained consciousness, and this provoked muscle responses in her hands and feet bilaterally. During the follow-up, the patient’s muscle tone became persistently flaccid, although her strength increased to varying degrees in different body and limb muscles. She remained bedridden for 3 years after the stroke and could neither turn on the bed by herself nor perform skilled movements using her hands. The findings of TMS confirmed the animal studies in that the mechanism of decerebrate rigidity did not come through a damage of the corticospinal pathway. This also implies that a preserved corticospinal tract function cannot guarantee a good motor recovery in a stroke patient