Cancer stem cells, bone and tumor microenvironment: Key players in bone metastases

Tumor mass is constituted by a heterogeneous group of cells, among which a key role is played by the cancer stem cells (CSCs), possessing high regenerative properties. CSCs directly metastasize to bone, since bone microenvironment represents a fertile environment that protects CSCs against the immune system, and maintains their properties and plasticity. CSCs can migrate from the primary tumor to the bone marrow (BM), due to their capacity to perform the epithelial-to-mesenchymal transition. Once in BM, they can also perform the mesenchymal-to-epithelial transition, allowing them to proliferate and initiate bone lesions. Another factor explaining the osteotropism of CSCs is their ability to recognize chemokine gradients toward BM, through the CXCL12\u2013CXCR4 axis, also known to be involved in tumor metastasis to other organs. Moreover, the expression of CXCR4 is associated with the maintenance of CSCs\u2019 stemness, and CXCL12 expression by osteoblasts attracts CSCs to the BM niches. CSCs localize in the pre-metastatic niches, which are anatomically distinct regions within the tumor microenvironment and govern the metastatic progression. According to the stimuli received in the niches, CSCs can remain dormant for long time or outgrow from dormancy and create bone lesions. This review resumes different aspects of the CSCs\u2019 bone metastastic process and discusses available treatments to target CSCs

PMMA-based bone cements and the problem of joint arthroplasty infections: Status and new perspectives

Polymethyl methacrylate (PMMA)-based bone cement is a biomaterial that has been used over the last 50 years to stabilize hip and knee implants or as a bone filler. Although PMMA-based bone cement is widely used and allows a fast-primary fixation to the bone, it does not guarantee a mechanically and biologically stable interface with bone, and most of all it is prone to bacteria adhesion and infection development. In the 1970s, antibiotic-loaded bone cements were introduced to reduce the infection rate in arthroplasty; however, the eciency of antibiotic-containing bone cement is still a debated issue. For these reasons, in recent years, the scientific community has investigated new approaches to impart antibacterial properties to PMMA bone cement. The aim of this review is to summarize the current status regarding antibiotic-loaded PMMA-based bone cements, fill the gap regarding the lack of data on antibacterial bone cement, and explore the progress of antibacterial bone cement formulations, focusing attention on the new perspectives. In particular, this review highlights the innovative study of composite bone cements containing inorganic antibacterial and bioactive phases, which are a fascinating alternative that can impart both osteointegration and antibacterial properties to PMMA-based bone cement

Composite xenohybrid bovine bone-derived scaffold as bone substitute for the treatment of tibial plateau fractures

Introduction: Tibial plateau fractures represent a common challenge for orthopaedic surgeons, sometimes representing complex cases to manage, where augmentation using bone grafts is required for stabilisation. Autologous iliac bone graft (AIBG) is the current gold standard for bone grafting. In order to overcome limitations related to the procedure, alternative strategies, like allogenic and xenogeneic bone substitutes have been investigated. Here, within the framework of an observational clinical study, we report clinical and radiological outcomes of patients treated for tibial plateau fractures with a composite xenohybrid bone graft, aiming at assessing clinical and radiological outcomes. Materials and Methods: We performed a cohort retrospective study of patients treated for tibial plateau fractures from May 2017 to January 2018. Thirty-four patients, i.e. 100% of those having received the bone graft under investigation for tibial plateaux fracture treatment, met the inclusion criteria and were enrolled in the study. Patients were assessed at 2 weeks, and then at a 1-, 3-, and 6-months, and 1-year follow-up. At each evaluation patients filled a visual analogue scale (VAS) for the level of pain during the day life activities and underwent physical exam and anteroposterior and lateral projection radiographs of the knee. At 1 year the Tegner Lysholm Scoring Scale, International Knee Document Committee 2000 (IKDC 2000), and Short Form (36) Health Survey (SF-36) were administered. Results: At 1-year, mean VAS decreased from 6.33 \ub1 1.40 to 1 \ub1 0.79 (P < 0.0001); Tegner Lysholm Scoring Scale was 89 \ub1 4.10 and mean IKDC 2000 was 78.67 \ub1 3.31. No infections, neurovascular complications or adverse effects related to implants werereported during the clinical exams at follow-up. Mean ROM was 124 \ub1 6\ub0. Radiographs did not show defects of consolidation or progressive post-surgical subsidence and demonstrated a good grade of integration of the implant. Conclusions: Clinical and radiological outcomes, and scores of questionnaires, were good. The xenograft has demonstrated to be a safe biomaterial, with satisfactory mechanical and biological performances in the mid-term period. It also showed a high grade of osteointegration and remodelling

Mineralization of 14C-diuron by Acinetobacter baumannii.

The diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is an herbicide used in sugarcane and other crops. This work evaluated the mineralization of the herbicide diuron by Acinetobacter baumannii and also was developed protocols for extraction and quantification of 14C-diuron. The strain (D12-12), isolated from rhizosphere of sugarcane, grown in soils treated with the herbicide, was cultivated in mineral media J.E. plus diuron at 20 ug/ml and plus 14C-diuron (specific activity = 2.43 MBq/mg) applied at 39,3215 KBq/50 ml, and incubated for 32 days in duplicate. The 14C-diuron extraction was carried out on C-18 SEP-PAK columns, resuspended in scintillation cocktail and the activity determined by liquid scintillation counting. The recuperation of diuron was more than 96,2% and 14CO2 accumulated after 32 days was 1,77%

Métodos de extração de hidrocarbonetos policíclicos aromáticos em amostra de solo, sedimento e lodo.

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Osteogenic differentiation modulates the cytokine, chemokine, and growth factor profile of ASCs and SHED

Great efforts have been made to improve bone regeneration techniques owing to a growing variety of sources of stem cells suitable for autologous transplants. Specifically, adipose-derived stem cells (ASCs) and stems cells from human exfoliated deciduous teeth (SHED) hold great potential for bone tissue engineering and cell therapy. After a preliminary characterization of the main biomolecules ASCs and SHED released in their conditioned media, cells were kept both in normal and osteo-inducing conditions. Conventional assays were performed to prove their osteogenic potential such as quantitative real-time polymerase chain reaction (qRT-PCR) (for RUNX-2, collagen type I, osteopontin and osteonectin), alkaline phosphatase activity, osteocalcin production, and von Kossa staining. Conditioned media were tested again after the osteogenic induction and compared to maintaining condition both at base line and after 14 days of culture. The osteogenic condition inhibited the release of all the biomolecules, with the exception, concerning SHED, of growth-regulated alpha protein precursor (GRO\u3b1), and, to a lesser extent, interleukin (IL)-8. In conclusion, our data support that undifferentiated ASCs and SHED may be preferable to committed ones for general cell therapy approaches, due to their higher paracrine activity. Osteoinduction significantly affects the cytokine, chemokine, and growth factor profile in a differential way, as SHED kept a more pronounced pro-angiogenic signature than ASCs

Bactérias promotoras de crescimento isoladas da rizosfera do feijoeiro.

Várias condições ambientais limitam a fixação simbiótica do N2 pelo feijoeiro. Por ser uma cultura muito utilizada por pequenos agricultores, as adubações nitrogenada e fosfatada não são feitas de forma adequadas, resultando na maioria das vezes em queda da produtividade. A utilização de rizobactérias promotoras do crescimento de planta (RPCP) tem surgido como técnica promissora para aumentar a produtividade do feijoeiro. Este trabalho teve como objetivo isolar RPCPs com capacidade para solubilizar fosfato e também como antagônicas a determinadas doenças do feijoeiro. Das 172 bactérias isoladas apenas 23 mostraram-se capazes de solubilizar fosfato em meio de cultura. No teste de antagonismo, somente o isolado T62 mostrou potencial para controle da antracnose (C.lindemuthianum) e da murcha do fusarium (Fusarium oxysporum f.sp. phaseoli)