Tumor cell-derived PDGF-B potentiates mouse mesenchymal stem cells-pericytes transition and recruitment through an interaction with NRP-1

<p>Abstract</p> <p>Background</p> <p>New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells and pericytes are essential steps in tumor angiogenesis. However, the role of tumor cells in differentiation and recruitment of mural cells has not yet been fully elucidated. This study focuses on the role of human tumor cells in governing the differentiation of mouse mesenchymal stem cells (MSCs) to pericytes and their recruitment in the tumor angiogenesis process.</p> <p>Results</p> <p>We show that C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of different tumor cell-derived conditioned media, differentiate into mature pericytes. These differentiated pericytes, in turn, are recruited to bind with capillary-like networks formed by endothelial cells on the matrigel under <it>in vitro </it>conditions and recruited to bind with blood vessels on gel-foam under <it>in vivo </it>conditions. The degree of recruitment of pericytes into <it>in vitro </it>neo-angiogenesis is tumor cell phenotype specific. Interestingly, invasive cells recruit less pericytes as compared to non-invasive cells. We identified tumor cell-secreted platelet-derived growth factor-B (PDGF-B) as a crucial factor controlling the differentiation and recruitment processes through an interaction with neuropilin-1 (NRP-1) in mesenchymal stem cells.</p> <p>Conclusion</p> <p>These new insights into the roles of tumor cell-secreted PDGF-B-NRP-1 signaling in MSCs-fate determination may help to develop new antiangiogenic strategies to prevent the tumor growth and metastasis and result in more effective cancer therapies.</p

Magnetic Behavior in RRhX (R = rare earths; X=B, C) Compounds

We report on the magnetic behavior of RRhB (R = La, Ce, Pr, Nd, Gd, Tb and Tm) and RRhC (R = La, Ce, Pr and Gd) compounds crystallizing in the cubic perovskite type structure with space group Pm3m. The heat capacity data on Pauli-paramagnetic LaRhB and LaRhC indicate a high frequency vibrating motion of boron and carbon atoms in the unit cell. Ce is in -like nonmagnetic state in both the compounds. Pr compounds show a dominant crystal field effect with a nonmagnetic singlet ground state in PrRhB and a nonmagnetic quadrupolar doublet in PrRhC. Compounds with other rare earths order ferromagnetically at low temperatures except TmRhB in which the zero field evolution of magnetic interactions is relatively more complicated. The electrical resistivity of GdRhB decreases with increasing temperature in the paramagnetic state in the vicinity of T, which is rarely seen in ferromagnets. The behavior is discussed to be arising due to the short range spin fluctuation and a possible contribution from Fermi surface geometry.Comment: 14 Figs and a text fil

The elephant in the room: Exploring the influence and participation of patients in infection-related care across surgical pathways in South Africa and India

Data availability statement: Data on which this publication is based are available via a secure server. Access to the data can be provided upon reasonable request. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.Copyright © 2023 The Authors. Objective: The irrational use of antibiotics is a leading contributor to antibiotic resistance. Antibiotic stewardship (AS) interventions predominantly focus on prescribers. This study investigated the influence and participation of inpatients in infection-related care, including antibiotic decision-making, within and across two tertiary hospitals in South Africa (Cape Town) and India (Kerala). Methods: Through ethnographic enquiry of clinical practice in surgical pathways, including direct nonparticipant observation of clinical practices, healthcare worker (HCW), patient and carer interactions in surgical ward rounds and face-to-face interviews with participants (HCWs and patients), we sought to capture the implicit and explicit influence that patients and carers have in infection-related care. Field notes and interview transcripts were thematically coded, aided by NVivo 12® Pro software. Results: Whilst observational data revealed the nuanced roles that patients/carers play in antibiotic decision-making, HCWs did not recognize these roles. Patients and carers, though invested in patient care, are not routinely involved, nor are they aware of the opportunities for engagement in infection-related decision-making. Patients associated clinical improvement with antibiotic use and did not consider hospitalization to be associated with infection acquisition or transmission, highlighting a lack of understanding of the threat of infection and antibiotic resistance. Patients' economic and cultural positionalities may influence their infection-related behaviours. In the study site in India, cultural norms mean that carers play widespread but unrecognized roles in inpatient care, participating in infection prevention activities. Conclusion: For patients to have a valuable role in AS and make informed decisions regarding their infection-related care, a mutual understanding of their role in this process among HCWs and patients is crucial. The observed differences between the two study sites indicate the critical need for understanding and addressing the contextual drivers that impact effective patient-centred healthcare delivery. Patient or Public Contribution: Ethnographic observations and interviews conducted in this study involved patients as participants. Patients were recruited for interviews after obtaining signed informed consent forms. Patients' identities were completely anonymized when presenting the study findings.Economic and Social Research Council. Grant Number: ES/P008313/1