The microbiome research field has rapidly evolved over the last few decades, becoming a major topic of scientific and public interest. The gut microbiota (GM) is the microbial population living in the gut. The GM has many functions, such as maintaining gut homeostasis and host health, providing defense against enteric pathogens, and involvement in immune system development. Several studies have shown that GM is implicated in dysbiosis and is presumed to contribute to neurodegeneration. This review focuses mainly on describing the connection between the intestinal microbiome alterations (dysbiosis) and the onset of neurodegenerative diseases to explore the mechanisms that link the GM to nervous system health, such as the gut-brain axis, as well as the mitochondrial, the adaptive humoral immunity, and the microvesicular pathways. The gut-brain communication depends on a continuous bidirectional flow of molecular signals exchanged through the neural and the systemic circulation. These pathways represent a possible new therapeutic target against neuroinflammation and neurodegeneration. Progress in this context is desperately needed, considering the severity of most neurodegenerative diseases and the current lack of effective treatments.

Metabolic Syndrome (MetS) is an extremely complex disease. A non-balanced diet such as high-fat diet (HFD) induces metabolic dysfunction that could modify redox homeostasis. We here aimed at exploring redox homeostasis in male Wistar rats, following 8 weeks of HFD, correlating the eventual modification of selected biomarkers that could be associated with the clinical manifestations of MetS. Therefore, we selected parameters relative to both the glucose tolerance and lipid altered metabolism, but also oxidative pattern. We assessed some biomarkers of oxidative stress i.e., thiols balance, lipid peroxidation and antioxidant barriers, via the use of specific biochemical assays, individuating eventual cross correlation with parameters relative to MetS through a Principal Component Analysis (PCA). The present study shows that 8 weeks of HFD induce MetS in rats, altering glucose and lipid homeostasis and increasing visceral adipose tissue, but also impairing the physiological antioxidant responses that could not counteract the oxidative stress condition. Crucially, cross-correlation analysis suggested that the assessment of specific oxidative stress parameters reported here can provide information comparable to the more widely acquired biomarkers of Mets such as glucose tolerance. Lastly, hepatic steatosis in association with the oxidative stress condition was also highlighted by histological analysis. This research will elucidate the fundamental impact of these oxidative stress parameters on MetS induced in the HFD rat model, tracing paths for developing prevention approaches.

Cancers reprogram macrophages (MΦs) to a tumor-growth-promoting TAM (tumor-associated MΦ) phenotype that is similar to the anti-inflammatory M2 phenotype. Poly(ADP-ribose) polymerase (PARP) enzymes regulate various aspects of MΦ biology, but their role in the development of TAM phenotype has not yet been investigated. Here, we show that the multispectral PARP inhibitor (PARPi) PJ34 and the PARP14 specific inhibitor MCD113 suppress the expression of M2 marker genes in IL-4-polarized primary murine MΦs, in THP-1 monocytic human MΦs, and in primary human monocyte-derived MΦs. MΦs isolated from PARP14 knockout mice showed a limited ability to differentiate to M2 cells. In a murine model of TAM polarization (4T1 breast carcinoma cell supernatant transfer to primary MΦs) and in a human TAM model (spheroids formed from JIMT-1 breast carcinoma cells and THP-1-MΦs), both PARPis and the PARP14 KO phenotype caused weaker TAM polarization. Increased JIMT-1 cell apoptosis in co-culture spheroids treated with PARPis suggested reduced functional TAM reprogramming. Protein profiling arrays identified lipocalin-2, macrophage migration inhibitory factor, and plasminogen activator inhibitor-1 as potential (ADP-ribosyl)ation-dependent mediators of TAM differentiation. Our data suggest that PARP14 inhibition might be a viable anticancer strategy with a potential to boost anticancer immune responses by reprogramming TAMs.

Over the last ten years, with the progress of in vitro culture methods, it has been possible to build increasingly reliable models to effectively mimic in vivo ones. The translational methodological approach that combined biotechnology and biomedical engineering has produced remarkable results, such as the development of ex vivo 3D culture models, the construction of on-a-chip organoids, and the construction of complex systems capable of bypassing the static nature of the two-dimensional cultural models that have been typical of in vitro studies conducted to date. However, nowadays, there is still reluctance to completely abandon the animal model as an essential reference or as an integrated step for the validation of a model or a proposed study. This is due to the partially correct conviction of the impossibility of reproducing, in vitro or ex vivo, the complexity of pathological models or the spatial communication between different cytotypes, as well as, more generally, the lack of systems capable of mimicking the dynamism of a complex in vivo system. In this study, we will compare different methodological approaches in the study of the three most common types of respiratory diseases: chronic obstructive pulmonary disease (COPD), asthma, and lung carcinomas. The purpose of this comparative study is to evaluate the most current methodological approaches to understand how far research is from being independent from animal models. Animal studies are generally considered necessary, but are still questioned because of the ethics and the cost–benefit ratio involved.

Laryngeal squamous cell carcinoma (LSCC) constitutes a noteworthy subset of head and neck cancers, contributing to about 4.5% of all malignancies. Its clinical behavior and characteristics exhibit variations contingent upon the specific anatomical site affected, with the glottis, supraglottis, and subglottis emerging as the most prevalent locations. Notably, squamous cell carcinoma represents a predominant histological type, accounting for 85% to 95% of all laryngeal cancers. The gender disparity is evident, with a higher incidence among males, exhibiting a ratio of 3.9:1. Moreover, disparities among racial groups are observed, as African American patients tend to manifest the condition at a younger age, coupled with lower overall survival rates compared to their Caucasian, Hispanic, and Asian counterparts. The primary etiological factors implicated in the onset of laryngeal cancer are tobacco and alcohol consumption, with a direct correlation to the intensity and duration of usage. Importantly, the risk diminishes gradually following cessation, necessitating a substantial period of at least 15 years for a return to baseline rates. Given the diverse nature of laryngeal SCC, treatment modalities are tailored based on the specific site and stage of the disease. Therapeutic interventions, such as radiotherapy, transoral laser microsurgery, open horizontal partial laryngectomy, or total laryngectomy, are employed with the overarching goal of preserving organ function. This study delves into the intricate realm of laryngeal SCC, specifically exploring the involvement of heat shock proteins (HSPs) in disease progression. This research meticulously examines the expression levels of Hsp10, Hsp27, Hsp60, and Hsp90 in dysplastic and benign tissue samples extracted from the right vocal cord, utilizing immunohistochemistry analysis. The focal point of the investigation revolves around unraveling the intricate role of these molecular chaperones in tissue differentiation mechanisms and cellular homeostasis, particularly within the inflammatory milieu characteristic of the tumor phenotype. The findings from this study serve as a robust histopathological foundation, paving the way for more in-depth analyses of the underlying mechanisms governing the contribution of the four chaperones to the development of squamous cell carcinoma in the larynx. Additionally, the data gleaned from this research hint at the potential of these four chaperones as valuable biomarkers, not only for diagnostic purposes but also for prognostication and ongoing patient monitoring. As our understanding of the molecular intricacies deepens, the prospect of targeted therapeutic interventions and personalized treatment strategies for laryngeal SCC becomes increasingly promising.

Laryngeal squamous cell carcinoma (SCC) is a head and neck cancer (about 5% of all cancers, and up to 95% of laryngeal cancers; more frequent in males than in females, ratio of 3.9/1) with characteristics depending on its location, with glottis, supraglottis, and subglottis being the most frequent. In African Americans, it appears at younger ages and has lower survival rates than in Caucasians, Hispanics, and Asians. Primary risk factors are tobacco and alcohol consumption. Treatments vary based on the site and stage of the tumor and include radiotherapy, transoral laser microsurgery, and surgery, including partial or total laryngectomy. This study aimed to map by immunohistochemistry four members of the Chaperone System (CS), namely Hsp10, Hsp27, Hsp60, and Hsp90, in laryngeal tissue during the progression from healthy stage to full malignancy, passing through dysplasia. The four chaperones increased in the tissues and changed distribution with the progression of carcinogenesis. The findings provide a histopathological platform for launching in-depth analyses of the mechanisms underpinning the role of the four chaperones in the development of squamous cell carcinoma of the larynx. Also, the data indicate that the four chaperones have potential as biomarkers for diagnosis, prognostication, and patient follow-up.