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Background: Autophagy is a self-degrading process. Previously, we showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel transforming growth factor β1 (TGFβ1)-interacting factor in liver fibrosis; the role of TGFβ1-mediated autophagy in hepatic stellate cells (HSCs) activation has been investigated. However, whether autophagy is regulated by IGFBPrP1 remains unknown.Aims: We investigated the interactions among IGFBPrP1, autophagy, and activation of primary rat HSCs.Methods: Primary HSCs were separated from Sprague Dawley rats by two-step enzymatic digestion, and then, we overexpressed or inhibited IGFBPrP1 expression in HSCs under serum-starved condition. Autophagy inducer rapamycin or inhibitor 3-methyladenine (3MA) was used to assess the relationship between autophagy and HSCs activation.Results: We observed the expression of activation marker α-SMA and autophagy markers such as LC3B and Beclin1, which were significantly increased in HSCs treated with adenovirus vector harboring the IGFBPrP1 gene (AdIGFBPrP1) compared to cells cultured under serum-starved. In comparison, HSCs treated with shIGFBPrP1 showed opposite results. Furthermore, HSCs activation and autophagy increased when cells were treated with rapamycin, whereas opposite results were obtained when cells were treated with 3MA. AdIGFBPrP1 treatment downregulated the phosphorylation of Akt and mTOR.Conclusion: Autophagy was induced in IGFBPrP1-treated primary HSCs, and IGFBPrP1-induced autophagy promoted the activation of HSCs and extracellular matrix expression, the underlying mechanism of which may involve the phosphatidylinositide 3-kinase/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

RMI1 (RecQ-mediated genome instability protein 1) forms a conserved BTR complex with BLM, Topo IIIα, and RMI2, and its absence causes genome instability. It has been revealed that RMI1 localizes to nuclear foci with BLM and Topo IIIα in response to replication stress, and that RMI1 functions downstream of BLM in promoting replication elongation. However, the precise functions of RMI1 during replication stress are not completely understood. Here we report that RMI1 knockdown cells are hypersensitive to hydroxyurea (HU). Using comet assay, we show that RMI1 knockdown cells exhibit accumulation of broken DNAs after being released from HU treatment. Moreover, we demonstrate that RMI1 facilitates the recovery from activated checkpoint and resuming the cell cycle after replicative stress. Surprisingly, loss of RMI1 results in a failure of RAD51 loading onto DNA damage sites. These findings reveal the importance of RMI1 in response to replication stress, which could explain the molecular basis for its function in maintaining genome integrity. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the radiosensitizing efficacy of the poly-ADP-ribose polymerase (PARP) inhibitor, olaparib, and the Bloom syndrome protein (BLM) helicase inhibitor, ML216, in non-small cell lung cancer (NSCLC) cells., Methods: Radiosensitization of NSCLC cells was assessed by colony formation and tumor growth assays. Mechanistically, the effects of ML216, olaparib, and radiation on cell and tumor proliferation, DNA damage, cell cycle, apoptosis, homologous recombination (HR) repair, and non-homologous end joining (NHEJ) repair activity were determined., Results: Both olaparib and ML216 enhanced the radiosensitivities of olaparib-sensitive H460 and H1299 cells, which was seen as decreased surviving fractions and Rad51 foci, increased total DNA damage, and γH2AX and 53BP1 foci ( P < 0.05). The expressions of HR repair proteins were remarkably decreased in olaparib-treated H460 and H1299 cells after irradiation ( P < 0.05), while olaparib combined with ML216 exerted a synergistic radiosensitization effect on olaparib-resistant A549 cells. In addition to increases of double strand break (DSB) damage and decreases of Rad51 foci, olaparib combined with ML216 also increased pDNA-PKcs (S2056) foci, abrogated G2 cell cycle arrest, and induced apoptosis in A549 lung cancer after irradiation in vitro and in vivo ( P < 0.05). Moreover, Western blot showed that olaparib combined with ML216 and irradiation inhibited HR repair, promoted NHEJ repair, and inactivated cell cycle checkpoint signals both in vitro and in vivo ( P < 0.05)., Conclusions: Taken together, these results showed the efficacy of PARP and BLM helicase inhibitors for radiosensitizing NSCLC cells, and supported the model that BLM inhibition sensitizes cells to PARP inhibitor-mediated radiosensitization, as well as providing the basis for the potential clinical development of this combination for tumors intrinsically resistant to PARP inhibitors and radiotherapy., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2022 Cancer Biology & Medicine.)

Semiconductor phase transitions and plasma noble metal quantum dots (QDs) for visible-light-driven photocatalysts have attracted significant research interest. In this study, novel microwave hydrothermal and photo-reduction methods are proposed to synthesise a visible-light-driven plasma photocatalytic 1T@2H-MoS 2 /Ag composite. Photoelectrochemical results show that the introduction of the 1T phase and Ag significantly enhances the light response range and charge separation. The 1T phase can act as a co-catalyst to provide a high electron concentration. Ag QDs can effectively improve the light absorption and catalytic effect. The synergistic effect between the 1T@2H-MoS 2 microspheres and localised surface plasmon resonance of the Ag QDs can effectively enhance the photocatalytic activity of 1T@2H-MoS 2 /Ag. The developed 1T@2H-MoS 2 /Ag composite is superior, not only with respect to a visible-light photocatalytic degradation of conventional dyes, but also in the photocatalytic reduction of Cr(VI). Compared with 2H-MoS 2 , the catalytic efficiency of 1T@2H-MoS 2 /Ag for Cr(VI) and MB is increased by 81% and 41%, respectively. This study demonstrates that the introduction of 1T-MoS 2 and Ag QDs can significantly enhance the catalytic properties of 2H-MoS 2 . The microwave and photo-reduction technologies can be employed as green, safe, simple, and rapid methods for the synthesis of noble metal plasma composites.