A Cheap Metal for a "Noble" Task: Preparative and Mechanistic Aspects of Cycloisomerization and Cycloaddition Reactions Catalyzed by Low-Valent Iron Complexes

Reaction of ferrocene with lithium in the presence of either ethylene or COD allows the Fe(0)-ate complexes 1 and 4 to be prepared on a large scale, which turned out to be excellent catalysts for a variety of Alder-ene, [4+2], [5+2], and [2+2+2] cycloadditon and cycloisomerization reactions of polyunsaturated substrates. The structures of ferrates 1 and 4 in the solid-state reveal the capacity of the reduced iron center to share electron density with the ligand sphere. This feature, coupled with the kinetic lability of the bound olefins, is thought to be responsible for the ease with which different enyne or diyne substrates undergo oxidative cyclization as the triggering event of the observed skeletal reorganizations. This mechanistic proposal is corroborated by highly indicative deuterium labeling experiments. Moreover, it was possible to intercept two different products of an oxidative cyclization manifold with the aid of the Fe(+1) complex 6, which, despite its 17-electron count, also turned out to be catalytically competent in certain cases. The unusual cyclobutadiene complex 38 derived from 6 and tolane was characterized by X-ray crystallography

PDGFRα plays a crucial role in connective tissue remodeling.

Platelet derived growth factor (PDGF) plays a pivotal role in the remodeling of connective tissues. Emerging data indicate the distinctive role of PDGF receptor-α (PDGFRα) in this process. In the present study, the Pdgfra gene was systemically inactivated in adult mouse (α-KO mouse), and the role of PDGFRα was examined in the subcutaneously implanted sponge matrices. PDGFRα expressed in the fibroblasts of Pdgfra-preserving control mice (Flox mice), was significantly reduced in the sponges in α-KO mice. Neovascularized areas were largely suppressed in the α-KO mice than in the Flox mice, whereas the other parameters related to the blood vessels and endothelial cells were similar. The deposition of collagen and fibronectin and the expression of collagen 1a1 and 3a1 genes were significantly reduced in α-KO mice. There was a significantly decrease in the number and dividing fibroblasts in the α-KO mice, and those of macrophages were similar between the two genotypes. Hepatocyte growth factor (Hgf) gene expression was suppressed in Pdgfra-inactivated fibroblasts and connective tissue. The findings implicate the role of PDGFRα-dependent ECM and HGF production in fibroblasts that promotes the remodeling of connective tissue and suggest that PDGFRα may be a relevant target to regulate connective tissue remodeling

Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

To profile the messenger RNA (mRNA) expression for the 23 known genes of matrix metalloproteinases (MMPs), 19 genes of ADAMTS, 4 genes of tissue inhibitors of metalloproteinases (TIMPs), and ADAM genes 8, 10, 12, and 17 in normal, painful, and ruptured Achilles tendons. Tendon samples were obtained from cadavers or from patients undergoing surgical procedures to treat chronic painful tendinopathy or ruptured tendon. Total RNA was extracted and mRNA expression was analyzed by quantitative real-time reverse transcription–polymerase chain reaction, normalized to 18S ribosomal RNA. In comparing expression of all genes, the normal, painful, and ruptured Achilles tendon groups each had a distinct mRNA expression signature. Three mRNA were not detected and 14 showed no significant difference in expression levels between the groups. Statistically significant (P < 0.05) differences in mRNA expression, when adjusted for age, included lower levels of MMPs 3 and 10 and TIMP-3 and higher levels of ADAM-12 and MMP-23 in painful compared with normal tendons, and lower levels of MMPs 3 and 7 and TIMPs 2, 3, and 4 and higher levels of ADAMs 8 and 12, MMPs 1, 9, 19, and 25, and TIMP-1 in ruptured compared with normal tendons. The distinct mRNA profile of each tendon group suggests differences in extracellular proteolytic activity, which would affect the production and remodeling of the tendon extracellular matrix. Some proteolytic activities are implicated in the maintenance of normal tendon, while chronically painful tendons and ruptured tendons are shown to be distinct groups. These data will provide a foundation for further study of the role and activity of many of these enzymes that underlie the pathologic processes in the tendon

Radio-frequency capacitance spectroscopy of metallic nanoparticles.

Recent years have seen great progress in our understanding of the electronic properties of nanomaterials in which at least one dimension measures less than 100 nm. However, contacting true nanometer scale materials such as individual molecules or nanoparticles remains a challenge as even state-of-the-art nanofabrication techniques such as electron-beam lithography have a resolution of a few nm at best. Here we present a fabrication and measurement technique that allows high sensitivity and high bandwidth readout of discrete quantum states of metallic nanoparticles which does not require nm resolution or precision. This is achieved by coupling the nanoparticles to resonant electrical circuits and measurement of the phase of a reflected radio-frequency signal. This requires only a single tunnel contact to the nanoparticles thus simplifying device fabrication and improving yield and reliability. The technique is demonstrated by measurements on 2.7 nm thiol coated gold nanoparticles which are shown to be in excellent quantitative agreement with theory.The work in the UK has been supported by EPSRC. The work in Japan has been partially supported by Elements Strategy Initiative to Form a Core Research Center, funded by The Ministry of Education, Culture, Sports, Science and Technology (MEXT); the Collaborative Research Project of Materials and Structures Laboratory, Tokyo Institute of Technology; the Collaborative Research Program of the Institute for Chemical Research, Kyoto University; and the BK21 plus Program through the Ministry of Education, Science and Technology of Korea

Histological and ultrastructural evaluation of the early healing of the lateral collateral ligament epiligament tissue in a rat knee model

<p>Abstract</p> <p>Background</p> <p>In this study, we evaluated the changes which occurred in the epiligament, an enveloping tissue of the ligament, during the ligament healing. We assessed the association of epiligament elements that could be involved in ligament healing.</p> <p>Methods</p> <p>Thirty-two 8-month old male Wistar rats were used in this study. In twenty-four of them the lateral collateral ligament of the knee joint was surgically transected and was allowed to heal spontaneously. The evaluation of the epiligament healing included light microscopy and transmission electron microscopy.</p> <p>Results</p> <p>At the eight, sixteenth and thirtieth day after injury, the animals were sacrificed and the ligaments were examined. Our results revealed that on the eight and sixteenth day post-injury the epiligament tissue is not completely regenerated. Till the thirtieth day after injury the epiligament is similar to normal, but not fully restored.</p> <p>Conclusion</p> <p>Our study offered a more complete description of the epiligament healing process and defined its important role in ligament healing. Thus, we provided a base for new strategies in ligament treatment.</p

MnSOD downergulation induced by extremely low 0.1 mGy single and fractionated X-rays and microgravity treatment in human neuroblastoma cell line, NB-1

Copyright © 2015 JCBN. A human neuroblastoma cell line, was treated with 24 h of microgravity simulation by clinostat, or irradiated with extremely small X-ray doses of 0.1 or 1.0 mGy using single and 10 times fractionation regimes with 1 and 2 h time-intervals. A quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) examination was performed for apoptosis related factors (BAX, CYTC, APAF1, VDAC1-3, CASP3, CASP8, CASP9 P53, AIF, ANT1 and 2, BCL2, MnSOD, autophagy related BECN and necrosis related CYP-40. The qRT-PCR results revealed that microgravity did not result in significant changes except for a upregulation of proapoptotic VDAC2, and downregulations of proapoptotic CASP9 and antiapoptotic MnSOD. After 0.1 mGy fractionation irradiation, there was increased expression of proapoptotic APAF1 and downregulation of proapoptotic CYTC, VDAC2, VDAC3, CASP8, AIF, ANT1, and ANT2, as well as an increase in expression of antiapoptotic BCL2. There was also a decrease in MnSOD expression with 0.1 mGy fractionation irradiation. These results suggest that microgravity and low-dose radiation may decrease apoptosis but may potentially increase oxidative stress

CO_2, water, and sunlight to hydrocarbon fuels: a sustained sunlight to fuel (Joule-to-Joule) photoconversion efficiency of 1%

If we wish to sustain our terrestrial ecosphere as we know it, then reducing the concentration of atmospheric CO_2 is of critical importance. An ideal pathway for achieving this would be the use of sunlight to recycle CO_2, in combination with water, into hydrocarbon fuels compatible with our current energy infrastructure. However, while the concept is intriguing such a technology has not been viable due to the vanishingly small CO_2-to-fuel photoconversion efficiencies achieved. Herein we report a photocatalyst, reduced blue-titania sensitized with bimetallic Cu–Pt nanoparticles that generates a substantial amount of both methane and ethane by CO_2 photoreduction under artificial sunlight (AM1.5): over a 6 h period 3.0 mmol g^(−1) methane and 0.15 mmol g^(−1) ethane are obtained (on an area normalized basis 0.244 mol m^(−2) methane and 0.012 mol m^(−2) ethane), while no H_2 nor CO is detected. This activity (6 h) translates into a sustained Joule (sunlight) to Joule (fuel) photoconversion efficiency of 1%, with an apparent quantum efficiency of φ = 86%. The time-dependent photoconversion efficiency over 0.5 h intervals yields a maximum value of 3.3% (φ = 92%). Isotopic tracer experiments confirm the hydrocarbon products originate from CO_2 and water

Effect of cross exercise on quadriceps acceleration reaction time and subjective scores (Lysholm questionnaire) following anterior cruciate ligament reconstruction

Abstract Background Anterior cruciate ligament (ACL) injury or reconstruction can cause knee impairments and disability. Knee impairments are related to quadriceps performance – accelerated reaction time (ART) – and disability to performance of daily living activities which is assessed by questionnaires such as the Lysholm knee score. The purposes of this study were to investigate the effect of cross exercise, as supplementary rehabilitation to the early phase of ACL reconstruction: a) on quadriceps ART at the angles 45°, 60° and 90° of knee flexion and, b) on the subjective scores of disability in ACL reconstructed patients. Methods 42 patients who underwent ACL reconstruction were randomly divided into 3 groups, two experimental and one control. All groups followed the same rehabilitation program. The experimental groups followed 8 weeks of cross eccentric exercise (CEE) on the uninjured knee; 3 d/w, and 5 d/w respectively. Quadriceps ART was measured at 45°, 60° and 90° of knee flexion pre and nine weeks post-operatively using an isokinetic dynamometer. Patients also completed pre and post operatively the Lysholm questionnaire whereby subjective scores were recorded. Results Two factor ANOVA showed significant differences in ART at 90° among the groups (F = 4.29, p = 0.02, p Significant differences were also found in the Lysholm score among the groups (F = 4.75, p = 0.01, p Conclusion CEE showed improvements on quadriceps ART at 90° at a sequence of 3 d/w and in the Lysholm score at a sequence of 3 d/w and 5 d/w respectively on ACL reconstructed patients.</p

Intersection of inflammation and herbal medicine in the treatment of osteoarthritis

Herbal remedies and dietary supplements have become an important area of research and clinical practice in orthopaedics and rheumatology. Understanding the risks and benefits of using herbal medicines in the treatment of arthritis, rheumatic diseases, and musculoskeletal complaints is a key priority of physicians and their patients. This review discusses the latest advances in the use of herbal medicines for treating osteoarthritis (OA) by focusing on the most significant trends and developments. This paper sets the scene by providing a brief introduction to ethnopharmacology, Ayurvedic medicine, and nutrigenomics before discussing the scientific and mechanistic rationale for targeting inflammatory signalling pathways in OA by use of herbal medicines. Special attention is drawn to the conceptual and practical difficulties associated with translating data from in-vitro experiments to in-vivo studies. Issues relating to the low bioavailability of active ingredients in herbal medicines are discussed, as also is the need for large-scale, randomized clinical trial