Synthesis and characterization of novel scaffold for bone tissue engineering based on Whartons´s jelly

A composite is a material made of more than one component, and the bond between the components is on a scale larger than the atomic scale. The objective of the present study was to synthesize and perform the structural characterization and biological evaluation of a new biocomposite (BCO) based on a novel combination of an organic and an inorganic phase, for bone tissue engineering applications. The organic phase consisted of Wharton´s Jelly (WJ), which was obtained from embryonic tissue following a protocol developed by our laboratory. The inorganic phase consisted of bioceramic particles (BC), produced by sintering hydroxyapatite (HA) with β- tricalcium phosphate (β-TCP), and bioactive glass particles (BG). Each phase of the BCO was fully characterized by SEM, EDS, XRD and FTIR. Biocompatibility was evaluated in vivo in the tibiae of Wistar rats (n=40). Histological evaluation was performed at 0, 1, 7, 14, 30 and 60 days. XRD showed the phases corresponding to HA and β-TCP, whereas diffractogram of BG showed it to have an amorphous structure. EDS showed mainly Si and Na, Ca, P in BG, and Ca and P in HA and β-TCP. FTIR identified bonds between the organic and inorganic phases. From a mechanical viewpoint, the composite showed high flexural strength of 40.3±0.8MPa. The synthesized BCO exhibited adequate biocompatibility as shown by formation of lamellar type bone linked by BG and BC particles. The biomaterial presented here showed excellent mechanical and biocompatibility properties for its potential clinical use.Fil: Martinez, Cristian. Universidad de Buenos Aires. Facultad de Ingenieria. Instituto de Ingeniería Biomédica; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Anatomía Patológica; Argentina. Universidad Nacional de Cuyo. Facultad de Odontologia; ArgentinaFil: Fernández, Carlos. Universidad de Buenos Aires. Facultad de Ingenieria. Instituto de Ingeniería Biomédica; ArgentinaFil: Prado, Miguel Oscar. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ozols, Andres. Universidad de Buenos Aires. Facultad de Ingenieria. Instituto de Ingeniería Biomédica; ArgentinaFil: Olmedo, Daniel Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Anatomía Patológica; Argentin

Synchronous liver and peritoneal metastases from colorectal cancer: Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy combined with liver resection a feasible option?

BackgroundTraditionally, synchronous liver resection (LR), cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases have been contraindicated. Nowadays, clinical practice has promoted this aggressive treatment in selected cases. This study aimed to review surgical and survival results of an extensive surgical approach including CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) and LR. MethodsPubMed, EMBASE, and Web of Science databases were matched to find the available literature on this topic. The search period was limited to 10 years (January 2010-January 2021). A threshold of case series of 10 patients or more was applied. ResultsIn the search period, out of 114 studies found about liver and peritoneal metastases from colorectal cancer, we found 18 papers matching the inclusion criteria. Higher morbidity and mortality were reported for patients who underwent such an extensive surgical approach when compared with patients who underwent only cytoreductive surgery and HIPEC. Also, survival rates seem worse in the former than in the latter. ConclusionThe role of combined surgical strategy in patients with synchronous liver and peritoneal metastases from colorectal cancer remains controversial. Survival rates and morbidity and mortality seem not in favor of this option. A more accurate selection of patients and more restrictive surgical indications could perhaps help improve results in this subgroup of patients with limited curative options

Development of novel monoclonal antibodies against CD109 overexpressed in human pancreatic cancer.

Pancreatic cancer is one of the most aggressive and lethal types of cancer, and more effective therapeutic agents are urgently needed. Overexpressed cell surface antigens are ideal targets for therapy with monoclonal antibody (mAb)-based drugs, but none have been approved for the treatment of pancreatic cancer. Here, we report development of two novel mouse mAbs, KU42.33C and KU43.13A, against the human pancreatic cancer cell line BxPC-3. Using ELISA, flow cytometry, competitive assay and immunoprecipitation followed by mass spectrometry, we discovered that these two mAbs target two distinct epitopes on the external domain of CD109 that are overexpressed by varying amounts in human pancreatic cancer cell lines. Treatment with these two naked antibodies alone did not affect tumour cell growth or migration in vitro. Of the two mAbs, only KU42.33C was useful in determining the expression of CD109 in tumour cells by Western blot and immunohistochemistry. Interestingly, immunohistochemistry of human pancreatic carcinoma tissue arrays with mAb KU42.33C showed that 94% of the 65 human pancreatic adenocarcinoma cases were CD109 positive, with no expression in normal pancreatic tissues. Our results suggest that these two novel mAbs are excellent tools for determining the expression level of CD109 in the tumour specimens and sera of patients with a wide range of cancers, in particular pancreatic cancer, and for investigating its diagnostic, prognostic and predictive value. Further research is warranted and should aim to unravel the therapeutic potential of the humanised forms or conjugated versions of such antibodies in patients whose tumours overexpress CD109 antigen

Targeting the Monocyte–Macrophage Lineage in Solid Organ Transplantation

textabstractThere is an unmet clinical need for immunotherapeutic strategies that specifically target the active immune cells participating in the process of rejection after solid organ transplantation. The monocyte-macrophage cell lineage is increasingly recognized as a major player in acute and chronic allograft immunopathology. The dominant presence of cells of this lineage in rejecting allograft tissue is associated with worse graft function and survival. Monocytes and macrophages contribute to alloimmunity via diverse pathways: antigen processing and presentation, costimulation, pro-inflammatory cytokine production, and tissue repair. Cross talk with other recipient immune competent cells and donor endothelial cells leads to amplification of inflammation and a cytolytic response in the graft. Surprisingly, little is known about therapeutic manipulation of the function of cells of the monocyte-macrophage lineage in transplantation by immunosuppressive agents. Although not primarily designed to target monocyte-macrophage lineage cells, multiple categories of currently prescribed immunosuppressive drugs, such as mycophenolate mofetil, mammalian target of rapamycin inhibitors, and calcineurin inhibitors, do have limited inhibitory effects. These effects include diminishing the degree of cytokine production, thereby blocking costimulation and inhibiting the migration of monocytes to the site of rejection. Outside the field of transplantation, some clinical studies have shown that the monoclonal antibodies canakinumab, tocilizumab, and infliximab are effective in inhibiting monocyte functions. Indirect effects have also been shown for simvastatin, a lipid lowering drug, and bromodomain and extra-terminal motif inhibitors that reduce the cytokine production by monocytes-macrophages in patients with diabetes mellitus and rheumatoid arthritis. To date, detailed knowledge concerning the origin, the developmental requirements, and functions of diverse specialized monocyte-macrophage subsets justifies research for therapeutic manipulation. Here, we will discuss the effects of currently prescribed immunosuppressive drugs on monocyte/macrophage features and the future challenges

Influenza and respiratory syncytial virus in infants study (IRIS) of hospitalized and non-ill infants aged <1 year in four countries: study design and methods

Abstract Background This multi-country prospective study of infants aged <1 year aims to assess the frequency of influenza virus and respiratory syncytial virus (RSV) infections associated with hospitalizations, to describe clinical features and antibody response to infection, and to examine predictors of very severe disease requiring intensive care. Methods/Design We are enrolling a hospital-based cohort and a sample of non-ill infants in four countries (Albania, Jordan, Nicaragua, and the Philippines) using a common protocol. We are currently starting year 2 of a 2- to 3-year study and will enroll approximately 3,000 infants hospitalized for any acute illness (respiratory or non-respiratory) during periods of local influenza and/or RSV circulation. After informed consent and within 24 h of admission, we collect blood and respiratory specimens and conduct an interview to assess socio-demographic characteristics, medical history, and symptoms of acute illness (onset ≤10 days). Vital signs, interventions, and medications are documented daily through medical record abstraction. A follow-up health assessment and collection of convalescent blood occurs 3-5 weeks after enrollment. Influenza and RSV infection is confirmed by singleplex real time reverse transcriptase polymerase chain reaction (rRT-PCR) assays. Serologic conversion will be assessed comparing acute and convalescent sera using hemagglutination inhibition assay for influenza antibodies and enzyme-linked immunosorbent assay (ELISA) for RSV. Concurrent with hospital-based enrollment, respiratory specimens are also being collected (and tested by rRT-PCR) from approximately 1,400 non-ill infants aged <1 year during routine medical or preventive care. Discussion The Influenza and RSV in Infants Study (IRIS) promises to expand our knowledge of the frequency, clinical features, and antibody profiles of serious influenza and RSV disease among infants aged <1 year, quantify the proportion of infections that may be missed by traditional surveillance, and inform decisions about the potential value of existing and new vaccines and other prevention and treatment strategies.https://deepblue.lib.umich.edu/bitstream/2027.42/136185/1/12879_2017_Article_2299.pd