Effects of ultrasound on Transforming Growth Factor-beta genes in bone cells

Therapeutic ultrasound (US) is a widely used form of biophysical stimulation that is increasingly applied to promote fracture healing. Transforming growth factor-beta (TGF-beta), which is encoded by three related but different genes, is known to play a major part in bone growth and repair. However, the effects of US on the expression of the TGF-beta genes and the physical acoustic mechanisms involved in initiating changes in gene expression in vitro, are not yet known. The present study demonstrates that US had a differential effect on these TGF-beta isoforms in a human osteoblast cell line, with the highest dose eliciting the most pronounced up-regulation of both TGF-beta1 and TGF-beta3 at 1 hour after treatment and thereafter declining. In contrast, US had no effect on TGF-beta2 expression. Fluid streaming rather than thermal effects or cavitation was found to be the most likely explanation for the gene responses observed in vitro

The Hopf algebra structure of the Z3_3-graded quantum supergroup GLq,j(1∣1)_{q,j}(1|1)

In this work, we give some features of the Z$_3$-graded quantum supergroup

Oyster resources of Ashtamudi lake, South West Coast of India

Edible oysters of the genera Crassostrea and Saccostrea occur in the estuaries, backwaters and coastal areas of India. Crassostrea madrasensis is the dominan~ oyster along Indian coast. In the recent years, extensive surveys were conducted in the estuaries of Tamil Nadu to study the potential oyster resource (Rao et al . 1987; Sarvesan et al.. 1988; Thangavelu and Sanjeevaraj. 1988). Along the Kerala coast oyster beds are distributed in the coastal zones and estuaries

ErbB- and MUC1-targetted CAR-T cell immunotherapy of oral squamous cell carcinoma

Chimeric antigen receptor T (CAR-T) cell therapy has shown great success in treating B cell malignancies however, there are many challenges which limit their therapeutic efficacy in solid tumours. Immunotherapy of head and neck squamous cell carcinoma (HNSCC), and in particular, oral squamous cell carcinoma (OSCC), presents a unique set of challenges including lack of consistently expressed tumour associated antigens (TAAs) and the immunosuppressive tumour microenvironment (TME). Currently, there are few clinical trials investigating the use of CAR-T cells in HNSCC/OSCC however results from trials investigating similar solid tumours, such as breast cancer, can be adopted to help evaluate the use of CAR-T in this cancer. In this review, the process of CAR-T cell engineering, and different generations of these cells will be summarised, highlighting their potential use in treating HNSCC through targeting ErbB and MUC1; TAAs highly expressed by this solid tumour. Potential strategies including combination therapy, utilising both TAA-targeting CAR-Ts and immune checkpoint inhibitors, such as PD-L1, has been discussed, in an attempt to develop synergistic anti-tumour responses. In addition to this, the use of dual-targeting CAR-T cells, synthetic NOTCH (synNOTCH) receptors and alternative non-tumour targets of the TME have been reviewed. Such combination therapies have been shown to help limit solid tumour progression and enhance both the safety and efficacy of CAR-T cell immunotherapy, which may be adopted for the treatment and management of OSCC

In vitro 3D tissue modelling: Insights into ameloblastoma pathogenesis

Ameloblastoma is a rare, benign oral tumour. Tumours develop within the jaw bone and are highly destructive and invasive, with cells migrating into the jaw and surrounding soft tissue. This is a little-understood disease which if left untreated causes dramatic bone destruction and maxillofacial disfigurement. Current treatment is radical surgery, often resulting in extensive loss of function and tissue. An ameloblastoma-derived cell line, AM-1, has been established [1]. Cells were isolated from a human tumour and immortalised by the addition of HPV-16 DNA. This study aims to (i) make a 3D in vitro ameloblastoma disease model, using plastic-compressed collagen gel [2] seeded with AM-1 cells, and (ii) use this bone construct to characterise tissue remodelling, cell growth and invasiveness

Single unconfined compression of cellular dense collagen scaffolds for cartilage and bone tissue engineering

Cell seeded collagen matrix scaffolds have been extensively evaluated recently as potential systems for de-novo tissue regeneration and repair for a variety of tissue types. While collagen gels are biologically excellent as starting point scaffold materials, their use is limited by the lack of cohesive structure and inherently weak mechanical properties due to a high liquid content (>99%). An ingenious method of combining unconfined plastic compression (PC) with capillary action has shown that these scaffolds can be rapidly processed into tissue like structures, which can be immediately implanted into the host[1]. It has been shown that the rapid increase in fibrillar collagen density dramatically enhanced the mechanical properties of such scaffolds thus potentially eliminating the need for long term cellular action. This simple project investigated the effect of single unconfined compression on cartilage-cell seeded collagen matrices in terms of cell viability, proliferation and oxygen consumption

Collagen gel as a 3D in vitro tissue model for ameloblastoma studies

Ameloblastoma is a rare locally invasive epithelial odontogenic tumour of the jaw which can cause significant and debilitating bone destruction. In vitro studies of ameloblastoma are sparse in the literature, and little is known regarding patterns of ameloblastoma cell growth and invasion, as well as relevant gene and protein expression. This study aims to (i) use plastic-compressed collagen gels as a robust and relevant biomimetic to culture ameloblastoma cells in a 3D in vitro tissue model [1] and (ii) perform histology, immunohistochemistry (IHC) and gene expression assays to characterise tissue remodelling, cell growth and invasiveness

Effects of therapeutic ultrasound on osteoblast gene expression

Ultrasound (US) is commonly used as a physiotherapy aid for a number of types of injury to soft connective tissues and for fracture healing. However, the precise effects of therapeutic US on tissue healing processes are not clearly understood, although they are likely to involve changes in key cellular functions. The present study has therefore examined the effects of several US intensity levels on the activity of two bone-associated proteins, alkaline phosphatase (ALP) and osteopontin (OP) in a human cell line, MG63, using RT-PCR. ALP showed progressively higher expression with increasing US intensities, whereas OP responded differently, showing down-regulation at 120 mW/cm2, the lowest US exposure. OP expression was considerably less affected overall compared with the relative response of ALP to the same US doses. The results show that there is a differential response to therapeutic levels of US, since ALP and OP clearly exhibited gene-specific response profiles. These findings suggest that modifying the parameters of US exposure could be used to improve repair and regeneration processes and enhance the clinical efficacy of implanted biomaterials for tissue engineering

Discussion with reviewers

This paper introduces the culture preparation of ovine, bovine and human cancellous bone cores to be used in an explants model Zetos. The three dimensional (3D) bone cores were prepared and evaluated for all three animals. Bone cells in vivo constantly interact with each other, migratory cells, surrounding extracellular matrix (eCM) and interstitial fluid in a microenvironment, which continuously responds to various endogenous and exogenous stimuli