In vitro synergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells

INTRODUCTION: Bisphosphonates are mostly used in the treatment of bone metastases. They have been shown to act synergistically with other chemotherapeutic agents. It is not known, however, whether similar synergistic effects exist with radiation on breast cancer cells. METHODS: Human MCF-7 breast cancer cells were treated with up to 100 μM zoledronic acid, were irradiated with up to 800 cGy or were exposed to combinations of both treatments to determine the antiproliferative effects of zoledronic acid and radiation. RESULTS: Zoledronic acid and radiation caused a dose-dependent and time-dependent decrease in cell viability (approximate 50% growth inhibition values were 48 μM and 20 μM for 24 hours and 72 hours, respectively, for zoledronic acid and 500 cGy for radiation). A synergistic cytotoxic effect of the combination of zoledronic acid and radiation was confirmed by isobologram analysis. CONCLUSION: These data constitute the first in vitro evidence for synergistic effects between zoledronic acid and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with metastatic breast carcinoma

Enhanced hydrogen desorption from Mg (BH4)2 by combining nanoconfinement and a Ni catalyst

Magnesium borohydride (Mg(BH4)2) has been infiltrated into highly ordered mesoporous carbon (CMK3) containing dispersed Ni nanoparticles (Ni NPs) to investigate the possible synergetic effects of nanoconfinement and catalysis by Ni NPs. Ni NPs (5 wt%) were introduced into the CMK3 nanoscaffold (CMK3–Ni) then Mg(BH4)2 was slowly infiltrated into this prepared CMK3–Ni template to synthesize a CMK3–Ni confined (Mg(BH4)2) system (denoted as CMK3–Ni–Mg(BH4)2). Solid-state 11B NMR and FT-IR spectra confirmed that Mg(BH4)2 was in the pores of CMK3–Ni. Temperature-programmed desorption mass spectroscopy (TPD-MS) and pressure–composition–temperature (PCT) measurements were utilized to study the hydrogen desorption properties for this nanoconfined CMK3–Ni–Mg(BH4)2 system, which was demonstrated to be remarkably improved, e.g. the hydrogen desorption temperature was dramatically decreased and the release rate was significantly enhanced. The hydrogen started to be released from the CMK3–Ni–Mg(BH4)2 at a temperature of only 75 C (measured by TPD) and reached its peak release rate at a temperature of 155 C, compared with 270 C and above 350 C respectively from pure Mg(BH4)2. To the best of our knowledge, this is the first time Mg(BH4)2 decomposition has been realized at a temperature below 100 C, which is of great significance for the use of this material for practical hydrogen storage for proton exchange membrane fuel cells (PEMFCs)

Social support and help-seeking worldwide

Social support has long been associated with positive physical, behavioral, and mental health outcomes. However, contextual factors such as subjective social status and an individual’s cultural values, heavily influence social support behaviors (e.g., perceive available social support, accept support, seek support, provide support). We sought to determine the current state of social support behaviors and the association between these behaviors, cultural values, and subjective social support across regions of the world. Data from 6,366 participants were collected by collaborators from over 50 worldwide sites (67.4% or n = 4292, assigned female at birth; average age of 30.76). Our results show that individuals cultural values and subjective social status varied across world regions and were differentially associated with social support behaviors. For example, individuals with higher subjective social status were more likely to indicate more perceived and received social support and help-seeking behaviors; they also indicated more provision of social support to others than individuals with lower subjective social status. Further, horizontal, and vertical collectivism were related to higher help-seeking behavior, perceived support, received support, and provision of support, whereas horizontal individualism was associated with less perceived support and less help-seeking and vertical individualism was associated with less perceived and received support, but more help-seeking behavior. However, these effects were not consistently moderated by region. These findings highlight and advance the understanding of how cross-cultural complexities and contextual distinctions influence an individual's perception, processing, and practice of social support embedded in the changing social landscape.</p

TAC3/TACR3 Mutations Reveal Preferential Activation of Gonadotropin-Releasing Hormone Release by Neurokinin B in Neonatal Life Followed by Reversal in Adulthood

Context: Mutations in TAC3 and TACR3 (encoding neurokinin B and its receptor) have been identified in Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations have not yet been tested and genotype-phenotype correlations have not been established