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Endotoxemia remains a critical clinical dilemma due to high mortality rate provoked by the systemic inflammatory response, which often leads to sever hepatic injury and immune dysregulation. This study aimed at delineating the modulatory effect of fucoxanthin (FX) and γ-radiation (IR) on LPS-induced spleen and liver injury. LPS sensitized mice showed enhanced splenic and hepatic TLR4/NF-κB- signaling, suppressed splenic α-7nAchR-expression, activated hepatic RIPK/HMGB-1, impaired hepatic leptin/STAT-3 signaling, extensive oxidative stress, and marked apoptosis with sever degenerative histopathological examination. FX and/or IR protected liver and spleen against detrimental effects evoked by LPS. Overall, FX and/or IR exhibited protective effect against endotoxemia. [ABSTRACT FROM AUTHOR]

Bisphenol-A (BPA) and gamma-radiation are two risky environmental pollutants that human beings are exposed to in everyday life and consequently they threaten human health via inducing oxidative stress, inflammation, and eventually tissue damage. This study aims at appraising the protective effect of Boswellic Acid (BA) (250 mg/kg/day, orally) administration on BPA (150 mg/kg/day, i.p) and γ-irradiation (IR) (3 Gy/week for 4 weeks up to cumulative dose of 12 Gy/experimental course) for 4 weeks-induced damage to liver and heart tissues of rats. The present results indicated a significant improvement against damage induced by BPA and IR revealed in biochemical investigations (hepatic PPAR-α/P38 and cardiac ET-1/Calcineurin-A/NFATc1/P38) and histopathological examination of liver and heart. It could be concluded that BA possesses a protective effect against these two deleterious environmental pollutants which attracted major global concerns due to their serious toxicological impact on human health. [ABSTRACT FROM AUTHOR]

Background: Tumor-promoting factors (TPF) and metabolic reprogramming are hallmarks of cancer cell growth. This study is designed to combine the newly synthesized two nanocomposites DDM (HA-FA-2DG@DCA@MgO) and AF (HA-FA-Amygdaline@Fe2O3) with fractionated doses of radiotherapy (6 Gy-FDR; fractionated dose radiotherapy) to improve the efficiency of chemo-radiotherapy against breast cancer cell lines (BCCs; MCF-7 and MDA-MB-231). The physicochemical properties of each nanocomposite were confirmed using energy dispersive XRD, FTIR, HR-TEM, and SEM. The stability of DDMPlusAF was also examined, as well as its release and selective cellular uptake in response to acidic pH. A multiple-MTT assay was performed to evaluate the radiosensitivity of BCCs to DDMPlusAF at 3 Gy (single dose radiotherapy; SDR) and 6 Gy-FDR after 24, 48, and 72 h. Finally, the anti-cancer activity of DDMPlusAF with 6 Gy-FDR was investigated via assessing the cell cycle distribution and cell apoptosis by flow cytometry, the biochemical mediators (HIF-1α, TNF-α, IL-10, P53, PPAR-α, and PRMT-1), along with glycolytic pathway (glucose, HK, PDH, lactate, and ATP) as well as the signaling effectors (protein expression of AKT, AMPK, SIRT-1, TGF-β, PGC-1α, and gene expression of ERR-α) were determined in this study. Results: The stability of DDMPlusAF was verified over 6 days without nanoparticle aggregation. DDMPlusAF release and selectivity data revealed that their release was amenable to the acidic pH of the cancer environment, and their selectivity was enhanced towards BCCs owing to CD44 and FR-α receptors-mediated uptake. After 24 h, DDMPlusAF boosted the BCC radiosensitivity to 6 Gy-FDR. Cell cycle arrest (G2/M and pre-G1), apoptosis induction, modulation of TPF mediators and signaling effectors, and suppression of aerobic glycolysis, all confirmed DDMPlusAF + 6 Gy's anti-cancer activity. Conclusions: It could be concluded that DDMPlusAF exerted a selective cancer radiosensitizing efficacy with targeted properties for TPF and metabolic reprogramming in BCCs therapy. [ABSTRACT FROM AUTHOR]

Cancers are a major challenge to health worldwide. Spinel ferrites have attracted attention due to their broad theranostic applications. This study aimed at investigating the antimicrobial, antibiofilm, and anticancer activities of ebselen (Eb) and cerium-nanoparticles (Ce-NPs) in the form of ZnCexFe2−XO4 on human breast and colon cancer cell lines. Bioassays of the cytotoxic concentrations of Eb and ZnCexFe2−XO4, oxidative stress and inflammatory milieu, autophagy, apoptosis, related signalling effectors, the distribution of cells through the cell-cycle phases, and the percentage of cells with apoptosis were evaluated in cancer cell lines. Additionally, the antimicrobial and antibiofilm potential have been investigated against different pathogenic microbes. The ZOI, and MIC results indicated that ZnCexFe2−XO4; X = 0.06 specimen reduced the activity of a wide range of bacteria and unicellular fungi at low concentration including P. aeruginosa (9.5 mm; 6.250 µg/mL), S. aureus (13.2 mm; 0.390 µg/mL), and Candida albicans (13.5 mm; 0.195 µg/mL). Reaction mechanism determination indicated that after ZnCexFe2−xO4; X = 0.06 treatment, morphological differences in S.aureus were apparent with complete lysis of bacterial cells, a concomitant decrease in the viable number, and the growth of biofilm was inhibited. The combination of Eb with ZFO or ZnCexFe2−XO4 with γ-radiation exposure showed marked anti-proliferative efficacy in both cell lines, through modulating the oxidant/antioxidant machinery imbalance, restoring the fine-tuning of redox status, and promoting an anti-inflammatory milieu to prevent cancer progression, which may be a valuable therapeutic approach to cancer therapy and as a promising antimicrobial agent to reduce the pathogenic potential of the invading microbes. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) has a complex and heterogeneous etiology, and the emergence of resistance to conventional chemo-and radiotherapy results in unsatisfactory outcomes during BC treatment. Targeted nanomedicines have tremendous therapeutic potential in BC treatment over their free drug counterparts., Objective: Hence, this study aimed to evaluate the newly fabricated pH-sensitive multifunctional FAHA- Amygdalin@Fe 2 O 3 nano-core-shell composite (AF nanocomposite) and/or γ-radiation for effective localized BC therapy., Methods: The physicochemical properties of nanoparticles were examined, including stability, selectivity, responsive release to pH, cellular uptake, and anticancer efficacy. MCF-7 and MDA-MB-231 cells were treated with AF at the determined IC 50 doses and/or exposed to γ-irradiation (RT) or were kept untreated as controls. The antitumor efficacy of AF was proposed via assessing anti-proliferative effects, cell cycle distribution, apoptosis, and determination of the oncogenic effectors., Results: In a bio-relevant medium, AF nanoparticles demonstrated extended-release characteristics that were amenable to acidic pH and showed apparent selectivity towards BC cells. The bioassays revealed that the HA and FA-functionalized AF markedly hindered cancer cell growth and enhanced radiotherapy (RT) through inducing cell cycle arrest (pre-G1 and G2/M) and increasing apoptosis, as well as reducing the tumorigenicity of BCs by inhibiting Silent information regulation factor 1 (SIRT1) and restoring p53 expression, deactivating the Yes-associated protein (YAP)/ Transcriptional coactivator with PDZ-binding motif (TAZ) signaling axis, and interfering with the tumor growth factor- β(TGF- β)/SMAD3 and HIF-1α/VEGF signaling hub while up-regulating SMAD7 protein expression., Conclusion: Collectively, the novel AF alone or prior RT abrogated BC tumorigenicity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)