BioFactors最新文献

Neuroblastomas are the most common solid tumors outside of the brain that originate from immature neural crest cells, accounting for about 10% of all pediatric malignancies. The treatment for neuroblastomas involves a multimodal schedule, including surgery, radiation, chemotherapy, and immunotherapy. All these modalities are limited by side effects that might be severe, poor prognosis, and a high risk of recurrence. In the quest for additional therapeutic approaches, phytochemicals have attracted attention owing to their reported antitumor properties, safety, and multimechanistic mode of action. Several studies have used plant-derived bioactive compounds such as phenolics and flavonoids, suggesting modulation of biomolecules and signal transduction pathways involved in neuroblastoma. We reviewed the findings of recent preclinical and clinical studies demonstrating the effects of phytochemicals on neuroblastoma, shedding light on their molecular mechanism of action and potential therapeutic applications.

Radioresistance poses a significant obstacle in cancer treatment. Lotus seedpod extract (LSE) has demonstrated anticancer effects in various cancer cells. However, its potential against radioresistant tumors remains unclear. In this study, we aimed to investigate the effect of LSE on radioresistant breast cancer cells, explore the underlying mechanism, and identify the major constituents responsible for its cytotoxic effect. LSE, extracted using 70% ethanol, exhibited selective cytotoxic effects against radioresistant breast cancer cells compared with their parental cells. Chemical analysis identified quercetin and its derivatives, hyperoside and miquelianin, as the major constituents responsible for these selective effects. Notably, quercetin displayed the most potent cytotoxicity against radioresistant breast cancer cells compared with hyperoside and miquelianin. Further investigation revealed that these compounds inhibited the activation of DNA repair systems, leading to the accumulation of DNA damage and the induction of apoptosis. Importantly, they efficiently suppressed the expression of ACSL4, a factor previously associated with radioresistance. In an in vivo study, quercetin exhibited a significant suppression of tumor growth in radioresistant tumor-bearing mice. Taken together, our findings highlight the potential of LSE and its major constituents, quercetin and its derivatives, in overcoming radioresistance in breast cancer. This study provides compelling evidence to support the use of LSE as a medicinal source for the future adjunctive therapy to combat radioresistance in breast cancers.

Propolis is a natural resinous substance made by bees through mixing various plant sources. Propolis has been widely recognized as a functional food due to its diverse range of beneficial bioactivities. However, the therapeutic effects of consuming propolis against atopic dermatitis (AD) remain largely unknown. The current study aimed to investigate the potential efficacy of propolis against AD and explore the active compound as well as the direct molecular target. In HaCaT keratinocytes, propolis inhibited TNF-α-induced interleukin (IL)-6 and IL-8 secretion. It also led to a reduction in chemokines such as monocyte chemoattractant protein-1 (MCP-1) and macrophage-derived chemokine (MDC), while restoring the levels of barrier proteins, filaggrin and involucrin. Propolis exhibited similar effects in AD-like human skin, leading to the suppression of AD markers and the restoration of barrier proteins. In DNCB-induced mice, oral administration of propolis attenuated AD symptoms, improved barrier function, and reduced scratching frequency and transepidermal water loss (TEWL). In addition, propolis reversed the mRNA levels of AD-related markers in mouse dorsal skin. These effects were attributed to caffeic acid phenethyl ester (CAPE), the active compound identified by comparing major components of propolis. Mechanistic studies revealed that CAPE as well as propolis could directly and selectively target MKK4. Collectively, these findings demonstrate that propolis may be used as a functional food agent for the treatment of AD.

Limonene, a dietary monocyclic monoterpene commonly found in citrus fruits and various aromatic plants, has garnered increasing interest as a gastrointestinal protectant. This study aimed to assess the effects of limonene on intestinal epithelial barrier function and investigate the involvement of cannabinoid receptor type-1 (CB1R) in vitro. Additionally, the study focused on examining the metabolomic changes induced by limonene in the intestinal epithelial cells (Caco-2). Initial analysis of transepithelial electrical resistance (TEER) revealed that both l-limonene and d-limonene, isomers of limonene, led to a dose- and time-dependent increase in TEER in normal cells and those inflamed by pro-inflammatory cytokines mixture (CytoMix). Furthermore, both types of limonene reduced CytoMix-induced paracellular permeability, as demonstrated by a decrease in Lucifer yellow flux. Moreover, d-limonene and l-limonene treatment increased the expression of tight junction molecules (TJs) such as occludin, claudin-1, and ZO-1, at both the transcriptional and translational levels. d-Limonene upregulates E-cadherin, a molecule involved in adherens junctions (AJs). Mechanistic investigations demonstrated that d-limonene and l-limonene treatment significantly inhibited CB1R at the protein, while the mRNA level remained unchanged. Notably, the inhibitory effect of d-limonene on CB1R was remarkably similar to that of pharmacological CB1R antagonists, such as rimonabant and ORG27569. d-limonene also alters Caco-2 cell metabolites. A substantial reduction in β-glucose and 2-succinamate was detected, suggesting limonene may impact intestinal epithelial cells' glucose uptake and glutamate metabolism. These findings suggest that d-limonene's CB1R antagonistic property could effectively aid in the recovery of intestinal barrier damage, marking it a promising gastrointestinal protectant.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver alterations worldwide, being gut microbiota dysbiosis one of the contributing factors to its development. The aim of this research is to compare the potential effects of a viable probiotic (Lactobacillus rhamnosus GG) with those exerted by its heat-inactivated paraprobiotic counterpart in a dietary rodent model of NAFLD. The probiotic administration effectively prevented the hepatic lipid accumulation induced by a high-fat high-fructose diet feeding, as demonstrated by chemical (lower TG content) and histological (lower steatosis grade and lobular inflammation) analyses. This effect was mainly mediated by the downregulation of lipid uptake (FATP2 protein expression) and upregulating liver TG release to bloodstream (MTTP activity) in rats receiving the probiotic. By contrast, the effect of the paraprobiotic preventing diet-induced liver lipid accumulation was milder, and mainly derived from the downregulation of hepatic de novo lipogenesis (SREBP-1c protein expression and FAS activity) and TG assembly (DGAT2 and AQP9 protein expression). The obtained results demonstrate that under these experimental conditions, the effects induced by the administration of viable L. rhamnosus GG preventing liver lipid accumulation in rats fed a diet rich in saturated fat and fructose differ from those induced by its heat-inactivated paraprobiotic counterpart.

Apigenin, a dietary flavonoid, has gained increasing attention for its potential therapeutic applications in radiation protection and radiosensitization. Ionizing radiation (IR) can harm healthy cells, but as radiotherapy remains crucial in cancer treatment. Owing to the remarkable application of radiotherapy in the treatment of cancers, it is vital to protect healthy cells from radiation hazards while increasing the sensitivity of cancer cells to radiation. This article reviews the current understanding of apigenin's radioprotective and radiosensitive properties with a focuses on the involved signaling pathways and key molecular targets. When exposed to irradiation, apigenin reduces inflammation via cyclooxygenase-2 inhibition and modulates proapoptotic and antiapoptotic biomarkers. Apigenin's radical scavenging abilities and antioxidant enhancement mitigate oxidative DNA damage. It inhibits radiation-induced mammalian target of rapamycin activation, vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP), and STAT3 expression, while promoting AMPK, autophagy, and apoptosis, suggesting potential in cancer prevention. As a radiosensitizer, apigenin inhibits tumor growth by inducing apoptosis, suppressing VEGF-C, tumor necrosis factor alpha, and STAT3, reducing MMP-2/9 activity, and inhibiting cancer cell glucose uptake. Cellular and animal studies support apigenin's radioprotective and anticancer potential, making it a potential candidate for further research. Investigation into apigenin's therapeutic efficacy in diverse cancer types and radiation damage is essential.

Ninghua Wu, Wu Liu, Jiawen Wang, Yanqi Han, Yu Ye, Xiufen Liu, Yuandong Yu, Qingjie Chen, Yongfen Bao, Chao Liu, 2021. Berberine ameliorates neuronal AD-like change via activating Pi3k/PGCε pathway. BioFactors, 47(4), 587–599. https://doi.org/10.1002/biof.1725

In Figures 5E and 6C, the incorrect images were used in assembling the figures. The correct Figures 5 and 6 are now provided. The correction has no impact on the main conclusion.

B. González-Fernández, D.I. Sánchez, I. Crespo, B. San-Miguel, M. Álvarez, M.J. Tuñón, and J. González-Gallego, “ Inhibition of the SphK1/S1P Signaling Pathway by Melatonin in Mice with Liver Fibrosis and Human Hepatic Stellate Cells,” BioFactors 43, no. 2 (2016): 272–282, https://doi.org/10.1002/biof.1342.

The above article, published online on 1 November 2016 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Irene Diaz-Moreno; International Union of Biochemistry and Molecular Biology (IUBMB); and Wiley Periodicals LLC. Following publication, concerns were raised by a third party that portions of Figures 1A, 2A, and 3A were duplicated. Internal investigation confirmed the duplications in these figures, as well as in Figure 4A. The authors provided some of the original data, but these were not sufficient to resolve the concerns, and the authors were unable to provide a satisfactory explanation. The authors disagree with the retraction decision.

Inducing browning in white adipocytes has emerged as a promising therapeutic approach for addressing obesity. Bioactive that modulate the WAT microenvironment to induce trans browning in white adipocytes have been explored as a strategy to control unregulated lipid storage. However, relying on a single bioactive for modulating lipid metabolism has proven insufficient in obese individuals during human trials, because these compounds primarily activate a single biochemical pathway in promoting browning. Consequently, there is a growing emphasis on targeting multiple pathways to ensure a safe and effective browning process. The present study investigated the combinatorial effect of bioactives namely Apigenin and Resveratrol for activating multiple pathways for effective trans-browning of white adipocytes. The combination was seen to promote the browning more effectively than the single bioactive, as the combination simultaneously activated multiple signaling pathways to induce angiogenesis-mediated browning in primary white adipocytes isolated from obese mice. Activation of PI3K signaling via estrogen receptor-α-dependent pathway resulted in simultaneous activation of angiogenesis and trans browning in white adipocytes. The study provides valuable insights into the potential use of bioactives in combination with therapeutic intervention to improve the overall health of obese subjects by enhancing lipid metabolism by activating trans-differentiation of white adipocytes.