Synthesis of Pyrazoles by 1,3-Dipolar Cycloaddition under Aqueous Micellar Catalysis

Ethyl diazoacetate (EDA), which is easily prepared from ethyl glycinate and NaNO2, reacts in situ with alkynes in a water micelle environment without organic solvent to form pyrazoles. The reaction is pH dependent, as in the presence of protic catalysis (H2SO4 4%, pH 3.5) a mixture of 3,5- and 4,5-disubstituted pyrazoles was obtained, while, at pH 5.5, only the 3,5-disubstituted isomer was obtained. The presence of the surfactant TPGS-750-M was crucial to secure clean crude reaction mixtures and high yields of the products. The same protocol was successfully applied to the synthesis of substituted pyrazolines. © 2022 The Author

<b><i>Topoisomerase 1</i></b> Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients

Objective: Topoisomerase 1 (topo-1) is an important target for the treatment of metastatic colorectal cancer (CRC). The aim of the present study was to evaluate the correlation between topo-1 single-nucleotide polymorphisms (SNPs) and clinical outcome in metastatic CRC (mCRC) patients. Methods: With the use of specific software (PROMO 3.0), we performed an in silico analysis of topo-1 promoter SNPs; the rs6072249 and rs34282819 SNPs were included in the study. DNA was extracted from 105 mCRC patients treated with FOLFIRI ± bevacizumab in the first line. SNP genotyping was performed by real-time PCR. Genotypes were correlated with clinical parameters (objective response rate, progression-free survival, and overall survival). Results: No single genotype was significantly associated with clinical variables. The G allelic variant of rs6072249 topo-1 SNP is responsible for GC factor and X-box-binding protein transcription factor binding. The same allelic variant showed a nonsignificant trend toward a shorter progression-free survival (GG, 7.5 months; other genotypes, 9.3 months; HR 1.823, 95% CI 0.8904-3.734; p = 0.1). Conclusion: Further analyses are needed to confirm that the topo-1 SNP rs6072249 and transcription factor interaction could be a part of tools to predict clinical outcome in mCRC patients treated with irinotecan-based regimens

Primary tumor sidedness and benefit from FOLFOXIRI plus bevacizumab as initial therapy for metastatic colorectal cancer. Retrospective analysis of the TRIBE trial by GONO

Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status

an application of collaborative robots in a food production facility

Abstract Despite the food industry being a leading sector of the European economy, the level of penetration of automation is still low. The main reasons lie on the small margin of food items which does not encourage technological investments, the extremely spread vendors market i.e. mostly small and medium enterprises, and the high level of flexibility and care required to handle food products along production, packaging, and storage operations. Nevertheless, the advent of collaborative, small and flexible robots provides great opportunities for the design and development of new effective processes integrating the human flexibility with the efficiency of automation. This paper explores the impact of adopting collaborative robots in the food catering industry, by illustrating a case study developed for the end-of-line of a catering production system. A generalizable methodology is proposed to support the study of the technical and economic feasibility of the implementation of such technology. This methodology is intended to support managers of the food industry to analyse the constraints that limit the automation of a process and to measure the expected performance of the system in terms of throughput, ergonomics and economic benefits resulting from the adoption of collaborative robots

Met-activating genetically improved chimeric factor-1 promotes angiogenesis and hypertrophy in adult myogenesis

BACKGROUND: Myogenic progenitor cells (activated satellite cells) are able to express both HGF and its receptor cMet. After muscle injury, HGF-Met stimulation promotes activation and primary division of satellite cells. MAGIC-F1 (Met-Activating Genetically Improved Chimeric Factor-1) is an engineered protein that contains two human Met-binding domains that promotes muscle hypertrophy. MAGIC-F1 protects myogenic precursors against apoptosis and increases their fusion ability enhancing muscle differentiation. Hemizygous and homozygous Magic-F1 transgenic mice displayed constitutive muscle hypertrophy. METHODS: Here we describe microarray analysis on Magic-F1 myogenic progenitor cells showing an altered gene signatures on muscular hypertrophy and angiogenesis compared to wild-type cells. In addition, we performed a functional analysis on Magic-F1+/+ transgenic mice versus controls using treadmill test. RESULTS: We demonstrated that Magic-F1+/+ mice display an increase in muscle mass and cross-sectional area leading to an improvement in running performance. Moreover, the presence of MAGIC-F1 affected positively the vascular network, increasing the vessel number in fast twitch fibers. Finally, the gene expression profile analysis of Magic-F1+/+ satellite cells evidenced transcriptomic changes in genes involved in the control of muscle growth, development and vascularisation. CONCLUSION: We showed that MAGIC -F1-induced muscle hypertrophy affects positively vascular network, increasing vessel number in fast twitch fibers. This was due to unique features of mammalian skeletal muscle and its remarkable ability to adapt promptly to different physiological demands by modulating the gene expression profile in myogenic progenitors

Mini-invasive approach to preneoplastic and neoplastic endometrial lesions. Comparative study among histological, cytological and immunohistochemical diagnosis

Objective: To compare the accuracy of cytology plus immunoistochemistry vs histology in the preoperative diagnosis of endometrial malignancy. Methods: We prospectively analyzed 142 women with a proliferative endometrial lesion undergoing operative hysteroscopy (ISC): at the time of ISC, the fluid used for saline contrast sonohysterography (SCSH) was collected for cytological analysis and compared to histology. In 9 women a markers board (Notch-1+ER-\u3b1+PR-\u3b2) expression was analyzed semiquantitatively in term of presence and intensity, on both glandular and stromal samples. Results: Table 1 shows the comparison between cytological and histological diagnosis. ISC histological results Benign Lesions n=134 Malignant Lesions n=8 Endometrial Polyps n=124 Hypertrophy n=3 Typical hyperplasia n=7 Atypical hyperplasia n=4 Cancer n=4 CTM - 0 0 0 0 0 CTM + 0 0 0 0 3 SCSH cytological results Atypia - 116 3 6 1 0 Atypia + 2 0 0 3 3 Inadequate (5%) 5 (4 cervical cells) (1 scant sample) 0 1 (1 cervical cells) 0 1 (hypocellulated) Cytological sampling was inadequate in 7 cases (5%). The K value between cytology and histology was 98.4% for benign and 85.7% for malignant lesions. Notch-1 revealed a changing expression pattern: absent in benign lesions, focal and marked in atypical hyperplasia and widespread and marked in cancers. Moreover Notch-1 expression was mild and focal in originally cyto-hystologycal benign lesions which turned into atypical hyperplasia during follow up. In cancer cases, ER-\u3b1 and PR-\u3b2 were widespread and markedly expressed either in the glandular or stromal layer. Conclusions: Cytological analysis could be used as a screening test, at least for women at high surgical risk. Notch-1+ER-\u3b1+PR-\u3b2 expression could be predictive for the risk of endometrial malignancy even at an earlier stadium than hyperplasia and could be used to identify the glandular or stromal origin of cancer thus helping in identifying women at increased risk of malignancy

Guide cells support muscle regeneration and affect neuro-muscular junction organization

Muscular regeneration is a complex biological process that occurs during acute injury and chronic degeneration, implicating several cell types. One of the earliest events of muscle regeneration is the inflammatory response, followed by the activation and differentiation of muscle progenitor cells. However, the process of novel neuromuscular junction formation during muscle regeneration is still largely unexplored. Here, we identify by single-cell RNA sequencing and isolate a subset of vessel-associated cells able to improve myogenic differentiation. We termed them 'guide' cells because of their remarkable ability to improve myogenesis without fusing with the newly formed fibers. In vitro, these cells showed a marked mobility and ability to contact the forming myotubes. We found that these cells are characterized by CD44 and CD34 surface markers and the expression of Ng2 and Ncam2. In addition, in a murine model of acute muscle injury and regeneration, injection of guide cells correlated with increased numbers of newly formed neuromuscular junctions. Thus, we propose that guide cells modulate de novo generation of neuromuscular junctions in regenerating myofibers. Further studies are necessary to investigate the origin of those cells and the extent to which they are required for terminal specification of regenerating myofibers

development of a new clinical nomogram including velocity rate of disease progression to predict outcome in metastatic colorectal cancer patients treated with bevacizumab beyond progression a subanalysis from tribe trial

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