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Background: Cisplatin (CDDP) is a first-line chemotherapeutic drug for treating various cancers. However, CDDP also damages normal cells and causes many side effects. Recently, CDDP has been demonstrated to kill cancer cells by targeting mitochondria. Protecting mitochondria might be a potential therapeutic strategy for CDDP-induced side effects. β-Lapachone (β-lap), a recognized NAD+ booster, has been reported to regulate mitochondrial activity. However, it remains unclear whether maintaining mitochondrial activity is the key factor in the protective effects of β-lap in CDDP-treated normal cells.Purpose: In this study, the protective effects of β-lap on mitochondria against CDDP cytotoxicity in normal cells were evaluated.Study Design: In vitro cell models were used in this study, including 3T3 fibroblasts, human dermal fibroblasts, MCF-7 breast cancer cells, and MDA-MB-231 breast cancer cells.Methods: Cells were treated with CDDP and β-lap, and cell survival, NAD+, mitochondrial activity, autophagy, and ATP production were measured. Various inhibitors and siRNAs were used to confirm the key signal underlying the protective effects of β-lap.Results: The results demonstrated that β-lap significantly decreased CDDP cytotoxicity in normal fibroblasts. With various inhibitors and siRNAs, β-lap reduced CDDP-induced damage to normal fibroblasts by maintaining mitochondrial activity and increasing autophagy through the NQO1/NAD+/SIRT1 axis. Most importantly, the protective effects of β-lap in fibroblasts did not affect the therapeutic effects of CDDP in cancer cells. This study indicated that mitochondrial activity, energy production, and NQO1 levels might be crucial responses separating normal cells from cancer cells under exposure to CDDP and β-lap.Conclusion: β-lap could be a good synergistic drug for reducing the side effects of CDDP without affecting the anticancer drug effect. [ABSTRACT FROM AUTHOR]

β-Lapachone, a novel anticancer drug, induces various human carcinoma cells to undergo apoptotic cell death. However, we report here that, in human osteocarcinoma (U2-OS) cells, β-lapachone induces necrosis rather than apoptosis. β-Lapachone-induced necrotic cell death in U2-OS cells was characterized by propidium iodide uptake, cytochrome c release, a decreased mitochondrial membrane potential, and ATP depletion. The mitochondrial potential transition (MPT), including the reduction of the mitochondrial transmembrane potential and the release of mitochondrial cytochrome c, occurred in β-lapachone-treated cells; cotreatment of these cells with cyclosporin A, an inhibitor of MPT pore, failed to prevent necrotic cell death. This indicates that the MPT transition does not play a crucial role in this process. Furthermore, β-lapachone-induced necrosis was independent of oxidative stress and caspase activation. However, excessive poly(ADP-ribose) polymerase (PARP) activation and subsequent depletion of intracellular NAD+ and ATP were seen in β-lapachone-treated U2-OS cells. Cotreatment with a PARP inhibitor, 3-aminobenzamide, decreased β-lapachone-induced PARP activation and provided significant protection from necrosis by preventing depletion of intracellular NAD+ and ATP. Taken together, our results suggest that PARP plays an important role in the signaling pathway for β-lapachone-induced necrosis in U2-OS cells. [Copyright &y& Elsevier]

In this study, we report the preparation of CuCrO 2 and CeO 2 composite by a self-combustion glycine nitrate process. A binary composite of CuCrO 2 -CeO 2 nanopowder has been successfully prepared by a one-pot method, wherein the precursor solution was prepared by mixing glycine with an aqueous solution of blended (Cu-Cr-Ce) metal-nitrates. The as-prepared binary composite has high specific surface area and can be prepared without the use of expensive chemical reagents or reducing agents. The crystal phase structure and purity of the CuCrO 2 -CeO 2 binary composite were examined by X-ray diffraction analysis. The morphology of the CuCrO 2 -CeO 2 nanopowder was investigated using scanning electron microscopy and transmission electron microscopy (TEM). The BET surface area measurements showed that the nanopowder had a large surface area. The TEM studies confirmed that the average particle size of the CuCrO 2 -CeO 2 binary composite was in the range of 5–10 nm. [ABSTRACT FROM AUTHOR]

Objective: To assess whether child food allergy is associated with family food insecurity, overall, and across different income levels., Methods: We used the 2011-2018 National Health Interview Survey, a nationally representative cross-sectional survey. The exposure was child food allergy, and our main outcome was odds of family food insecurity, which was calculated using multivariable logistic regression models adjusted for child demographics, family characteristics and survey year. We examined for effect modification by the ratio of family income to the poverty threshold using stratification and tests for statistical interaction., Results: Among 83,287 children 6% had food allergy and 22% experienced family food insecurity. Child food allergy was associated with a 1.39-fold (95% confidence interval [CI]: 1.26, 1.53) increased odds of family food insecurity overall. Child food allergy was associated with a 1.46-fold (95% CI: 1.29, 1.66) increased odds of family food insecurity among children whose families lived below 200% of the federal poverty level, and a 1.26-fold (95% CI: 1.05, 1.51) increased odds of family food insecurity among children whose families lived at 200 to 399% of the federal poverty level, with no association among children whose families lived at or above 400% of the federal poverty level (P =.04 for interaction)., Conclusion: There is an association between child food allergy and family food insecurity, and this association is modified by the ratio of family income to the poverty threshold. Improved availability and subsidy of allergen-free foods in nutrition assistance programs and food pantries are urgently needed., Competing Interests: Declaration of Competing Interest SJC has a close family member employed by a Johnson & Johnson company and has served on advisory boards for Alexion Pharmaceuticals. KAK and a close family member owns stocks in pharmaceutical and health care companies. LCS has been an investigator for DBV Technologies, has received grants from Genentech, and has served on advisory boards for DBV Technologies, Alladapt Immunotherapeutics, and Ukko. KEW within the past 36 months has served as a consultant for Sanofi and Research Triangle Institute. As this publication is not related to medications, these may not be COIs. All other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Cisplatin (CDDP) is a first-line chemotherapeutic drug for treating various cancers. However, CDDP also damages normal cells and causes many side effects. Recently, CDDP has been demonstrated to kill cancer cells by targeting mitochondria. Protecting mitochondria might be a potential therapeutic strategy for CDDP-induced side effects. β-Lapachone (β-lap), a recognized NAD + booster, has been reported to regulate mitochondrial activity. However, it remains unclear whether maintaining mitochondrial activity is the key factor in the protective effects of β-lap in CDDP-treated normal cells., Purpose: In this study, the protective effects of β-lap on mitochondria against CDDP cytotoxicity in normal cells were evaluated., Study Design: In vitro cell models were used in this study, including 3T3 fibroblasts, human dermal fibroblasts, MCF-7 breast cancer cells, and MDA-MB-231 breast cancer cells., Methods: Cells were treated with CDDP and β-lap, and cell survival, NAD + , mitochondrial activity, autophagy, and ATP production were measured. Various inhibitors and siRNAs were used to confirm the key signal underlying the protective effects of β-lap., Results: The results demonstrated that β-lap significantly decreased CDDP cytotoxicity in normal fibroblasts. With various inhibitors and siRNAs, β-lap reduced CDDP-induced damage to normal fibroblasts by maintaining mitochondrial activity and increasing autophagy through the NQO1/NAD + /SIRT1 axis. Most importantly, the protective effects of β-lap in fibroblasts did not affect the therapeutic effects of CDDP in cancer cells. This study indicated that mitochondrial activity, energy production, and NQO1 levels might be crucial responses separating normal cells from cancer cells under exposure to CDDP and β-lap., Conclusion: β-lap could be a good synergistic drug for reducing the side effects of CDDP without affecting the anticancer drug effect., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Paired-like homeodomain transcription factor 2 ( PITX2 ) is well known to play an essential role in normal embryonic development. Emerging evidence suggests that PITX2 may be involved in human tumorigenesis, but the role of PITX2 in tumour progression remains largely unclear. The expression levels of PITX2 in lung cancer cells were determined by qRT-PCR and Western blot analyses. Gain- and loss-of-function experiments were conducted to investigate the biological roles of PITX2 in the phenotype of lung cancer cells. Immunofluorescence staining and transmission electron microscopy were used to observe autophagy. The expression level and clinical significance of PITX2 were determined in a Taiwanese cohort and the Gene Expression Omnibus (GEO) database, respectively. Here, we show that PITX2B is the most abundant isoform of the bicoid homeodomain family in lung cancer cells. The enforced expression of PITX2B promoted lung cancer tumorigenesis and progression in vitro and in vivo . The mechanistic analysis revealed that the nuclear localization of PITX2B is correlated with its oncogenic functions and two important nuclear localization signals. In addition, PITX2B knockdown in lung cancer cells caused a marked increase in autophagy and apoptosis, suggesting that PITX2B plays an important role in lung cancer cell survival. Moreover, a high expression of PITX2B was associated with a poor overall survival ( P <0.05) in both Taiwanese non-small-cell lung cancer patients and GEO lung cancer cohorts. These results provide new insight into the contribution of PITX2B to lung cancer progression, implicate PITX2B as an important component of cell survival signals and further establish PITX2B as a therapeutic target for lung cancer treatment., Competing Interests: None., (AJCR Copyright © 2021.)