Mesenchymal stem cells (MSC) exhibit tropism for sites of tissue damage as well as the tumor microenvironment. Many of the same inflammatory mediators that are secreted by wounds are found in the ...tumor microenvironment and are thought to be involved in attracting MSC to these sites. Cell migration is dependent on a multitude of signals ranging from growth factors to chemokines secreted by injured cells and/or respondent immune cells. MSC are likely to have chemotactic properties similar to other immune cells that respond to injury and sites of inflammation. Thus, the well-described model of leukocyte migration can serve as a reasonable example to facilitate the identification of factors involved in MSC migration. Understanding the factors involved in regulating MSC migration to tumors is essential to ultimately develop novel clinical strategies aimed at using MSC as vehicles to deliver antitumor proteins or suppress MSC migration to reduce tumor growth. For example, radiation enhances inflammatory signaling in the tumor microenvironment and may be used to potentiate site-specific MSC migration. Alternatively, restricting the migration of the MSC to the tumor microenvironment may prevent competent tumor-stroma formation, thereby hindering the growth of the tumor. In this review, we will discuss the role of inflammatory signaling in attracting MSC to tumors.
Ripening is a crucial step to guarantee the high commercial value of cheddar cheese, one of the dairy products the European Union exports the most. Although several methods have lately been proposed ...to assess its ageing process from a chemical point of view, the majority of them is not particularly time-efficient and implies destructive analytical tests, thus, exhibiting limitations for, e.g., industrial applications. Here, a fast approach based on combining Raman and Mid-InfraRed (MIR) spectroscopy with ANOVA-Simultaneous Component Analysis (ASCA) is proposed in a low-level data fusion framework. This approach allowed to evaluate how storage temperature and time (as well as their interaction) influence cheddar ripening in a relatively cheap, rapid and green fashion.
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•Raman and Mid-InfraRed (MIR) spectroscopic data fusion.•ANOVA-Simultaneous Component Analysis (ASCA) of low-level-fused data.•Study of storage temperature and ripening time influence on cheddar cheese ageing.•Proteo- and lypolisis phenomena highlighted in a rapid and non-destructive fashion.
Bisphenol A (BPA) is one of the most largely produced chemical in the world; it is used to make plastics and epoxy resins. The endocrine disruptor potential of BPA is well known, but recent ...researches suggest a relationship between chronic exposure to BPA, genotoxic activity and epigenetic modifications.
The main source of exposure to BPA includes food contact materials (FCM). Thus simple and robust test methods are needed to improve the migration test of BPA. In this work, a non-separative, easy, fast and inexpensive spectrofluorimetric method based on the second order calibration of excitation-emission fluorescence matrices (EEMs) was proposed for the determination of BPA. For the first time, molecular fluorescence was used to identify unequivocally and quantify BPA. Trilinearity of the data tensor guarantees the uniqueness of the solution obtained through parallel factor analysis (PARAFAC), so one factor of the decomposition matches up with BPA even if other fluorophores are in the test sample.
The effect of four experimental factors of the procedure on the figures of merit and the unequivocally identification was investigated by means of a D-optimal design and PARAFAC calibration. The method is linear and accurate in the range 0–720µgL−1. The decision limit CCα and detection capability CCβ are 6.63µgL−1 and 18.85µgL−1 respectively (with probabilities of false positive and false negative fixed at 0.05).
Finally the proposed method was applied to carry out a migration test from two polycarbonate cups, using 3% (w/v) acetic acid in aqueous solution as food simulant. The migrated amount of BPA was found to be 688.7µgL−1 (n=5) for the first cup and 710.5µgL−1 (n=4) for the second one, above the specific migration limit set by EFSA (European Food Safety Authority).
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•A procedure to determine bisphenol-A: rapid, cheap, and aligned with green chemistry.•Molecular fluorescence coupled to PARAFAC to identify and quantify bisphenol-A.•Robustness of the unequivocal identification of bisphenol-A versus several parameters.•Identification of Bisphenol-A migrated from polycarbonate cups to food simulant.
Herein, we disclose a general and flexible access to spirocyclopropyl oxindoles by a domino Michael/intramolecular nucleophilic substitution pathway with variously substituted vinyl selenones and ...enolizable oxindoles in aqueous sodium hydroxide solution. The spirocyclopropyl oxindole being a privileged scaffold, some of the synthesized compounds were selected for biological evaluation. Compound showed selective anti-HIV-1 activity thanks to its ability to inhibit the reverse transcriptase.
Summary
We analyzed polymorphism of the
ALPL
gene in patients with low serum levels of tissue-nonspecific alkaline phosphatase (TNAP). The presence of three or more of the less frequent alleles of
...ALPL
polymorphisms was associated with significantly lower TNAP serum level and higher frequencies of metatarsal fractures, which may help confirm a clinical suspicion of adult hypophosphatasia.
Introduction
Alkaline phosphatases (ALPs) are membrane-bound enzymes that hydrolyze monophosphate esters at a high pH (pH 8–10). Inorganic pyrophosphate, pyridoxal 5-phosphate, the activated form of vitamin B
6
(PLP), and phosphoethanolamine (PEA), are natural substrates of ALPs. Hypophosphatasia (HPP, OMIM 146300, 241500, 241510) is a heterogeneous rare metabolic bone disease caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase gene (
ALPL; MIM 171760
) with a deficiency of TNAP. Clinical presentation of HPP in adults demonstrated a wide range of manifestations, many of which are nonspecific. In the present study, we screened the polymorphic genetic variants of
ALPL
in 56 subjects presenting low serum levels of TNAP and/or other clinical signs of adult HPP in order to evaluate a possible role of polymorphic variants in the diagnosis and management of HPP in adults.
Methods
Genomic DNA was extracted from peripheral blood and
ALPL
gene was sequenced by PCR-based Sanger technique.
Results
Fourteen different polymorphic variants were found in the study population. A lower serum level of TNAP and higher frequencies of metatarsal fractures were observed in patients bearing three or more of the minor frequency alleles (MFAs) of the
ALPL
polymorphic variants. The presence of some MFAs, mostly as a contemporary presence of three or more of them, was found to be mainly represented in patients having both a significantly lower level of TNAP and a higher level of vitamin B6.
Conclusion
The genetic analysis and presence of some polymorphic variants may be an instrument to confirm clinical and biochemical data, consider adult HPP, and help clinicians be cautious in the administration of anti-reabsorption drugs.
KRAS is one of the most frequently mutated oncogenes in human non-small cell lung cancers (NSCLCs). RAS proteins trigger multiple effector signalling pathways including the highly conserved RAF-MAPK ...pathway. CRAF, a direct RAS effector protein, is required for KRAS-mediated tumourigenesis. Thus, the molecular mechanisms driving the activation of CRAF are intensively studied. Prohibitin 1 (PHB1) is an evolutionarily conserved adaptor protein and interaction of CRAF with PHB1 at the plasma membrane is essential for CRAF activation. Here, we demonstrate that PHB1 is highly expressed in NSCLC patients and correlates with poor survival. Targeting of PHB1 with two chemical ligands (rocaglamide and fluorizoline) inhibits epidermal growth factor (EGF)/RAS-induced CRAF activation. Consistently, treatment with rocaglamide inhibited proliferation, migration and anchorage-independent growth of KRAS-mutated lung carcinoma cell lines. Surprisingly, rocaglamide treatment inhibited Ras-GTP loading in KRAS-mutated cells as well as in EGF-stimulated cells. Rocaglamide treatment further prevented the oncogenic growth of KRAS-driven lung cancer allografts and xenografts in mouse models. Our results suggest rocaglamide as a RAS inhibitor and that targeting plasma membrane-associated PHB1 with chemical ligands would be a viable therapeutic strategy to combat KRAS-mediated NSCLCs.
We report the results of three mark-release-recapture experiments carried out in an urban area in Rome, Italy, to study the active dispersal of Aedes albopictus (Diptera: Culicidae). The 4.3% ...recapture rate obtained supports the use of sticky traps in MRR experiments to study the dispersal of Ae. albopictus females. Most fluorescent dust‐marked females were recaptured at the gravid stage at 50-200 m from the release sites during the first 9 days after release. The average of daily‐MDTs (Mean Distance Traveled) was 119 m and the maximum observed distance travelled ranged from 199 m to 290 m in the three replicates. These data provide the first information about the dispersal of Ae. albopictus in a temperate European area and appear to be consistent with the few data available on this subject from other urban areas, where dispersal was constrained by physical barriers. Although caution should be taken in generalizing these results, they should be considered when planning control activities in urban areas in Italy, as well as in other European countries. This is particularly relevant if control is intended to interrupt pathogen transmission in cases of possible arbovirus epidemics, such as the Chikungunya outbreak that occurred in Ravenna, Italy in 2007.
Recent evidence suggests that mesenchymal stem cells (MSC) selectively proliferate to tumors and contribute to the formation of tumor-associated stroma. The biological rationale for tumor recruitment ...of MSC remains unclear but may represent an effort of the host to blunt tumor cell growth and improve survival. There is mounting experimental evidence that normal stromal cells can revert malignant cell behavior, and separate studies have demonstrated that stromal cells can enhance tumor progression after acquisition of tumor-like genetic lesions. Together, these observations support the rationale for modifying normal MSC to deliver therapeutic proteins directly into the tumor microenvironment. Modified MSC can produce high concentrations of antitumor proteins directly within the Tumor mass, which have been shown to blunt tumor growth kinetics in experimental animal model systems. In this chapter we will address the biological properties of MSC within the tumor microenvironment and discuss the potential use of MSC and other bone marrow-derived cell populations as delivery vehicles for antitumor proteins.
Purpose
Radiofrequency (RF) treatment has played an increasing role in the management of benign thyroid nodules in recent years. The aim of this retrospective study was to evaluate the efficacy of RF ...treatment on volume reduction in functioning and non-functioning thyroid nodules.
Patients and methods
We reviewed the medical records of patients who had thyroid nodule RF ablation at our department between August 2017 and May 2018. Patients underwent a periodical follow-up with ultrasound examinations and thyroid function tests at 1, 3, 6 and 12 months from RF. Complications were assessed using the reporting standards of Interventional societies.
Results
43 patients were submitted to thyroid nodule RF ablation treatment. Patients were subdivided into two groups, those with functioning (17 patients) or non-functioning nodules. At baseline (i.e. pre-RF treatment), the two groups of patients were superimposable for gender, age, BMI, nodule volume and maximum nodule diameter. The volume reduction of all 43 nodules was 69.1 ± 17.3% (range 26.0–94.5%) with no difference between functioning and non-functioning lesions (72.9 ± 18.1% vs 66.7 ± 16.7%,
p
= 0.254). A total energy delivered per nodule was 16.5 ± 6.8 kJ, with no difference between functioning and non-functioning lesions (14.5 ± 7.2 kJ vs. 18.2 ± 6.3 kJ,
p
= 0.083, respectively). No major complications were observed.
Conclusions
Radiofrequency ablation is a clinically effective and safe outpatient treatment in patients with benign nodules. In particular, we showed that a single treatment is effective in restoring euthyroidism in patients with autonomously functioning thyroid nodules.
Summary
Achalasia is a rare disease with significant diagnostic delay and association with false diagnoses and unnecessary interventions. It remains unclear, whether atypical presentations, ...misinterpreted symptoms or inconclusive diagnostics are the cause. The aim of this study was the characterization of typical and atypical features of achalasia and their impact on delays, misinterpretations or false diagnoses. A retrospective analysis of prospective database over a period of 30 years was performed. Data about symptoms, delays and false diagnoses were obtained and correlated with manometric, endoscopic and radiologic findings. Totally, 300 patients with achalasia were included. Typical symptoms (dysphagia, regurgitation, weight loss and retrosternal pain) were present in 98.7%, 88%, 58.4% and 52.4%. The mean diagnostic delay was 4.7 years. Atypical symptoms were found in 61.7% and led to a delay of 6 months. Atypical gastrointestinal symptoms were common (43%), mostly ‘heartburn’ (16.3%), ‘vomiting’ (15.3%) or belching (7.7%). A single false diagnosis occurred in 26%, multiple in 16%. Major gastrointestinal misdiagnoses were GERD in 16.7% and eosinophilic esophagitis in 4%. Other false diagnosis affected ENT-, psychiatric, neurologic, cardiologic or thyroid diseases. Pitfalls were the description of ‘heartburn’ or ‘nausea’. Tertiary contractions at barium swallows, hiatal hernias and ‘reflux-like’ changes at endoscopy or eosinophils in the biopsies were misleading. Atypical symptoms are common in achalasia, but they are not the sole source for diagnostic delays. Misleading descriptions of typical symptoms or misinterpretation of diagnostic studies contribute to false diagnoses and delays.
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