Oral treatment with herbal formula B307 alleviates skeletal muscle atrophy from hind-limb unloading

PosterINTRODUCTION: Muscle atrophy can result from physical inactivity, chronic bedrest, and ageing. Traditional Chinese herbal formula B307 is a health supplement with multiple potential protective functions of organs. We investigated the effects of herbal formula B307 on muscle atrophy using the hind-limb unloading (HU) model in mice …published_or_final_versio

Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.

Connective tissue diseases of the skin are characterized by excessive collagen deposition in the skin and internal organs. Fibroblasts play a pivotal role in the clinical presentation of these conditions. Nuclear receptor peroxisome-proliferator activated receptors (PPARs) are therapeutic targets for dermal fibrosis, but the contribution of the different PPAR subtypes are poorly understood. Particularly, the role of fibroblast PPARβ/δ in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPARβ/δ in the fibroblast (FSPCre- <i>Pparb/d</i> <sup>-/-</sup> ) and interrogated its epidermal and dermal transcriptome profiles. We uncovered a downregulated gene, leucine-rich alpha-2-glycoprotein-1 ( <i>Lrg1</i> ), of previously unknown function in skin development and architecture. Our findings suggest that the regulation of <i>Lrg1</i> by PPARβ/δ in fibroblasts is an important signaling conduit integrating PPARβ/δ and TGFβ1-signaling networks in skin health and disease. Thus, the FSPCre- <i>Pparb/d</i> <sup>-/-</sup> mouse model could serve as a novel tool in the current gunnery of animal models to better understand dermal fibrosis

Prostate transglutaminase (TGase-4) antagonizes the anti-tumour action of MDA-7/IL-24 in prostate cancer

Background Transglutamiase-4 (TGase-4), also known as prostate transglutaminase, belongs to the TGase family and is uniquely expressed in the prostate gland. The functions of this interesting protein are not clearly defined. In the present study, we have investigated an unexpected link between TGase-4 and the melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24), a cytokine known to regulate the growth and apoptosis of certain cancer and immune cells. Methods Frozen sections of normal and malignant human prostate tissues and human prostate cancer (PCa) cell lines PC-3 and CA-HPV-10, cell lines expressing low and high levels of TGase-4, and recombinant MDA-7/IL-24 (rhMDA-7/IL-24) were used. Expression construct for human TGase-4 was generated using a mammalian expression vector with full length human TGase-4 isolated from normal human prostate tissues. PC-3 cells were transfected with expression construct or control plasmid. Stably transfected cells for control transfection and TGase-4 over expression were created. Similarly, expression of TGase-4 in CA-HPV-10 cells were knocked down by way of ribozyme transgenes. Single and double immunofluorescence microscopy was used for localization and co-localization of TGase-4 and MDA-7/IL-24 in PCa tissues and cells with antibodies to TGase-4; MDA-7/IL-24; IL-20alpha; IL-20beta and IL-22R. Cell-matrix adhesion, attachment and migration were by electric cell substrate impedance sensing and growth by in vitro cell growth assay. A panel of small molecule inhibitors, including Akt, was used to determine signal pathways involving TGase-4 and MDA-7/IL-24. Results We initially noted that MDA-7 resulted in inhibition of cell adhesion, growth and migration of human PCa PC-3 cells which did not express TGase-4. However, after the cells over-expressed TGase-4 by way of transfection, the TGase-4 expressing cells lost their adhesion, growth and migratory inhibitory response to MDA-7. On the other hand, CA-HPV-10 cells, a cell type naturally expressing high levels of TGase-4, had a contrasting response to MDA-7 when compared with PC-3 cells. Inhibitor to Akt reversed the inhibitory effect of MDA-7, only in PC-3 control cells, but not the TGase-4 expressing PC-3 cells. In human prostate tissues, TGase-4 was found to have a good degree of co-localization with one of the MDA-7 receptor complexes, IL-20Ra. Conclusion The presence of TGase-4 has a biological impact on a prostate cancer cell's response to MDA-7. TGase-4, via mechanism(s) yet to be identified, blocked the action of MDA-7 in prostate cancer cells. This has an important implication when considering the use of MDA-7 as a potential anticancer cytokine in prostate cancer therapies

1-phenyl 2-thiourea (PTU) activates autophagy in zebrafish embryos

202207 bcwwAccepted ManuscriptOthersHMRFPublishe

A Bayesian conditional autoregressive geometric process model for range data

Extreme value theories indicate that the range is an efficient estimator of local volatility in financial time series. A geometric process (GP) framework that incorporates the conditional autoregressive range (CARR)-type mean function is presented for range data. The proposed model, called the conditional autoregressive geometric process range (CARGPR) model, allows for flexible trend patterns, threshold effects, leverage effects, and long-memory dynamics in financial time series. For robustness considerations, a log-t distribution is adopted. Model implementation can be easily done using the WinBUGS package. A simulation study shows that model parameters are estimated with high accuracy. In the empirical study on the range data of an Australian stock market index, the CARGPR model outperforms the CARR model in both in-sample estimation and out-of-sample forecast. © 2010 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex

Leukocyte invasion of the brain after peripheral trauma in zebrafish (Danio rerio)

202309 bcvcVersion of RecordOthersFish Model Translational Research Laboratory; University of Hong KongPublishe