Therefore, this review summarizes recent studies on the identification and understanding of DAMPs, their receptors, and cross-talk between the liver and other organs, and highlights successful therapeutic targets and potential strategies in drug development that can be used to combat ALD.Complex patterns of normal faults with multiple orientations and/or highly curved shapes have been traditionally explained by successive tectonic phases of 2-dimensional deformation. Alternatively, multiple fault sets have been proposed to develop simultaneously and in orthorhombic symmetry during a single phase of 3-dimensional deformation. We use analogue models of normal faults to demonstrate that, without the influence of pre-existing structures, 3D extension is preferentially accommodated by the alternate, rather than simultaneous, development of faults with different trends. By means of stress-driven interactions, 3D deformation can be partitioned into coupled systems of normal faults, which display geometries commonly observed in tectonic settings affected by interacting plate boundaries. Under radial extension, deformation is accommodated by major curvilinear grabens coupled with minor perpendicular faults, resulting in the triple junctions of grabens observed in Afar. On the other hand, the alternate development of perpendicular faults accommodates synchronous bi-directional and mutually perpendicular extension, giving the same fault pattern observed in the Barents Sea rift-shear margin.There is increasing evidence about the use of oncolytic adenoviruses (Ads) as promising immunotherapy agents. We have previously demonstrated the clinical efficiency of mesenchymal stem cells (MSCs) infected with oncolytic Ads as an antitumoral immunotherapy (called Celyvir) in human and canine patients, using ICOVIR-5 or ICOCAV17 as human and canine oncolytic Ads, respectively. Considering the better clinical outcomes of canine patients, in this study we searched for differences in cellular responses of human and canine MSCs to Ad infection that may help understand the mechanisms leading to higher antitumor immune response. We found that infection of human and canine MSCs with ICOVIR-5 or ICOCAV17 did not activate the NF-κB pathway or the interferon regulatory factors IRF3 and IRF7. However, we observed differences in the profile of cytokines secretion, as infection of canine MSCs with ICOCAV17 resulted in lower secretion of several cytokines. Moreover, we showed that infection of human MSCs with ICOVIR-5 increased the phosphorylation of a number of proteins, including AKT and c-JUN. Finally, we demonstrated that differences in regulation of AKT and c-JUN in human and canine MSCs by ICOVIR-5 or ICOCAV17 are intrinsic to each virus. Our findings suggest that ICOCAV17 induces a more limited host response in canine MSCs, which may be related to a better clinical outcome. This result opens the possibility to develop new human oncolytic Ads with these specific properties. In addition, this improvement could be imitated by selecting specific human MSC on the basis of a limited host response after Ad infection.Cancer immunotherapy has revolutionised cancer treatment, with immune checkpoint blockade (ICB) therapy and adoptive cell therapy (ACT) increasingly becoming standard of care across a growing number of cancer indications. While the majority of cancer immunotherapies focus on harnessing the anti-tumour CD8+ cytotoxic T cell response, the potential role of CD4+ 'helper' T cells has largely remained in the background. In this review, we give an overview of the multifaceted role of CD4+ T cells in the anti-tumour immune response, with an emphasis on recent evidence that CD4+ T cells play a bigger role than previously thought. We illustrate their direct anti-tumour potency and their role in directing a sustained immune response against tumours. We further highlight the emerging observation that CD4+ T cell responses against tumours tend to be against self-derived epitopes. These recent trends raise vital questions and considerations that will profoundly affect the rational design of immunotherapies to leverage on the full potential of the immune system against cancer.Ferroptosis has become a topic of rapidly growing interest in recent years, and has possible therapy implications in cancer therapy. Although excessive autophagy may contribute to ferroptosis, its underlying molecular mechanism remains largely unknown. Cirtuvivint Here, we provide novel evidence that the interplay between the signals of mechanistic target of rapamycin kinase (MTOR) and glutathione peroxidase 4 (GPX4) modulates autophagy-dependent ferroptosis in human pancreatic cancer cells. Both the classical autophagy inducer rapamycin and the classical ferroptosis activator RSL3 can block MTOR activation and cause GPX4 protein degradation in human pancreatic cancer cells. Moreover, GPX4 plays an essential role in the inhibition of autophagy-dependent ferroptosis induced by rapamycin and RSL3. Consequently, GPX4 depletion by RNAi enhances the anticancer activity of rapamycin and RSL3 in vitro or in vivo. These findings not only increase our understanding of stress responses in cell death, but may also raise the possibility of developing new antitumor therapy targeting autophagy-dependent cell death.Recent efforts have revealed that long non-coding RNAs exert crucial roles in cancer initiation and progression. RHPN1-AS1 is a 2030 bp transcript from human chromosome 8q24, and involved in tumorigenesis in uveal melanoma and non-small cell lung cancer, but it remains unknown in ovarian cancer. This study focused on the role of RHPN1-AS1 in ovarian cancer and found that RHPN1-AS1 was up-regulated in ovarian cancer tissues and cell lines. Overexpression of RHPN1-AS1 promoted ovarian cancer cell proliferation, migration, and invasion. Mechanistically, overexpression of RHPN1-AS1 decreased the expression of miR-665 and subsequently promoted the expression of Akt3 at posttranscriptional level. Taken together, RHPN1-AS1 positively regulated the expression of Akt3 through sponging miR-665, and exerted an oncogenic role in ovarian cancer progression, and indicates that RHPN1-AS1 may be a potential therapeutic target in ovarian cancer.