Peritoneal fibrosis is characterized by abnormal production of extracellular matrix proteins leading to progressive thickening of the submesothelial compact zone of the peritoneal membrane. This process may be caused by a number of insults including pathological conditions linked to clinical practice, such as peritoneal dialysis, abdominal surgery, hemoperitoneum, and infectious peritonitis. All these events may cause acute/chronic inflammation and injury to the peritoneal membrane, which undergoes progressive fibrosis, angiogenesis, and vasculopathy. Among the cellular processes implicated in these peritoneal alterations is the generation of myofibroblasts from mesothelial cells and other cellular sources that are central in the induction of fibrosis and in the subsequent functional deterioration of the peritoneal membrane. Myofibroblast generation and activity is actually integrated in a complex network of extracellular signals generated by the various cellular types, including leukocytes, stably residing or recirculating along the peritoneal membrane. Here, the main extracellular factors and the cellular players are described with emphasis on the cross-talk between immune system and cells of the peritoneal stroma. The understanding of cellular and molecular mechanisms underlying fibrosis of the peritoneal membrane has both a basic and a translational relevance, since it may be useful for setup of therapies aimed at counteracting the deterioration as well as restoring the homeostasis of the peritoneal membrane.

In recent years, progress in nanotechnology provided new tools to treat cancer more effectively. Advances in biomaterials tailored for drug delivery have the potential to overcome the limited selectivity and side effects frequently associated with traditional therapeutic agents. While autophagy is pivotal in determining cell fate and adaptation to different challenges, and despite the fact that it is frequently dysregulated in cancer, antitumor therapeutic strategies leveraging on or targeting this process are scarce. This is due to many reasons, including the very contextual effects of autophagy in cancer, low bioavailability and non-targeted delivery of existing autophagy modulatory compounds. Conjugating the versatile characteristics of nanoparticles with autophagy modulators may render these drugs safer and more effective for cancer treatment. Here, we review current standing questions on the biology of autophagy in tumor progression, and precursory studies and the state-of-the-art in harnessing nanomaterials science to enhance the specificity and therapeutic potential of autophagy modulators.

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Autophagy and the lysosomal system, together referred to as the autophagolysosomal system, is a cellular quality control network which maintains cellular health and homeostasis by removing cellular waste including protein aggregates, damaged organelles, and invading pathogens. As such, the autophagolysosomal system has roles in a variety of pathophysiological disorders, including cancer, neurological disorders, immune- and inflammation-related diseases, and metabolic alterations, among others. The autophagolysosomal system is controlled by TFEB, a master transcriptional regulator driving the expression of multiple genes, including autophagoly sosomal components. Importantly, Reactive Oxygen Species (ROS) production and control are key aspects of the physiopathological roles of the autophagolysosomal system, and may hold a key for synergistic therapeutic interventions. In this study, we reviewed our current knowledge on the biology and physiopathology of the autophagolysosomal system, and its potential for therapeutic intervention in cancer.

Although lung fibrosis has a major impact in COVID-19 disease, its pathogenesis is incompletely understood. In particular, no direct evidence of pleura implication in COVID-19-related fibrotic damage has been reported so far. In this study, the expression of epithelial cytokeratins and Wilms tumor 1 (WT1), specific markers of mesothelial cells (MCs), was analyzed in COVID-19 and unrelated pleura autoptic samples. SARS-CoV-2 replication was analyzed by RT-PCR and confocal microscopy in MeT5A, a pleura MC line. SARS-CoV-2 receptors were analyzed by RT-PCR and western blot. Inflammatory cytokines from the supernatants of SARS-CoV-2-infected MeT5A cells were analysed by Luminex and ELLA assays. Immunohistochemistry of COVID-19 pleura patients highlighted disruption of pleura monolayer and fibrosis of the sub-mesothelial stroma, with the presence of MCs with fibroblastoid morphology in the sub-mesothelial stroma, but no evidence of direct infection in vivo. Interestingly, we found evidence of ACE2 expression in MCs from pleura of COVID-19 patients. In vitro analysis shown that MeT5A cells expressed ACE2, TMPRSS2, ADAM17 and NRP1, plasma membrane receptors implicated in SARS-CoV-2 cell entry and infectivity. Moreover, MeT5A cells sustained SARS-CoV-2 replication and productive infection. Infected MeT5A cells produced interferons, inflammatory cytokines and metalloproteases. Overall, our data highlight the potential role of pleura MCs as promoters of the fibrotic reaction and regulators of the immune response upon SARS-CoV-2 infection.

The Dominican Republic is one of the two countries on the Hispaniola island, which is part of the Antilles. Hispaniola was interested by the European colonisation and massive deportation of African slaves since the XVI century and these events heavily shaped the genetic composition of the present-day population. In order to shed light about the effect of the European rules, we analysed 92 SNPs on the Y chromosome in 182 Dominican individuals from three different locations. The Dominican Y haplogroup composition was characterised by an excess of northern African/European lineages (59%), followed by the African clades (38%), while the Native-American lineages were rare (3%). The comparison with the mtDNA variability, dominated by African clades, revealed a sex-biased admixture pattern, in line with the colonial society dominated by European men. When other Caribbean and non-Caribbean former colonies were also considered, we noted a difference between territories under a Spanish rule (like the Dominican Republic) and British/French rule, with the former characterised by an excess of European Y lineages reflecting the more permissive Iberian legislation about mixed people and slavery. Finally, we analysed the distribution in Africa of the Dominican lineages with a putative African origin, mainly focusing on central and western Africa, which were the main sources of African slaves. We found that most (83%) of the African lineages observed in Santo Domingo have a central African ancestry, suggesting that most of the slaves were deported from regions

Chronic kidney disease (CKD) incidence is growing worldwide, with a significant percentage of CKD patients reaching end-stage renal disease (ESRD) and requiring kidney replacement therapies (KRT). Peritoneal dialysis (PD) is a convenient KRT presenting benefices as home therapy. In PD patients, the peritoneum is chronically exposed to PD fluids containing supraphysiologic concentrations of glucose or other osmotic agents, leading to the activation of cellular and molecular processes of damage, including inflammation and fibrosis. Importantly, peritonitis episodes enhance peritoneum inflammation status and accelerate peritoneal injury. Here, we review the role of immune cells in the damage of the peritoneal membrane (PM) by repeated exposure to PD fluids during KRT as well as by bacterial or viral infections. We also discuss the anti-inflammatory properties of current clinical treatments of CKD patients in KRT and their potential effect on preserving PM integrity. Finally, given the current importance of coronavirus disease 2019 (COVID-19) disease, we also analyze here the implications of this disease in CKD and KRT.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) control gene expression by acting at multiple levels and are often deregulated in epithelial tumors; however, their roles in the fine regulation of cellular reprogramming, specifically in epithelial–mesenchymal transition (EMT), remain largely unknown. Here, we focused on the hnRNP-Q (also known as SYNCRIP), showing by molecular analysis that in hepatocytes it acts as a “mesenchymal” gene, being induced by TGFβ and modulating the EMT. SYNCRIP silencing limits the induction of the mesenchymal program and maintains the epithelial phenotype. Notably, in HCC invasive cells, SYNCRIP knockdown induces a mesenchymal–epithelial transition (MET), negatively regulating their mesenchymal phenotype and significantly impairing their migratory capacity. In exploring possible molecular mechanisms underlying these observations, we identified a set of miRNAs (i.e., miR-181-a1-3p, miR-181-b1-3p, miR-122-5p, miR-200a-5p, and miR-let7g-5p), previously shown to exert pro- or anti-EMT activities, significantly impacted by SYNCRIP interference during EMT/MET dynamics and gathered insights, suggesting the possible involvement of this RNA binding protein in their transcriptional regulation.