Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activation

Rationale: Loss of histone macroH2A1 induces appearance of cancer stem cells (CSCs)-like cells in hepatocellular carcinoma (HCC). How CSCs interact with the tumor microenvironment and the adaptive immune system is unclear. Methods: We screened aggressive human HCC for macroH2A1 and CD44 CSC marker expression. We also knocked down (KD) macroH2A1 in HCC cells, and performed integrated transcriptomic and secretomic analyses. Results: Human HCC showed low macroH2A1 and high CD44 expression compared to control tissues. MacroH2A1 KD CSC-like cells transferred paracrinally their chemoresistant properties to parental HCC cells. MacroH2A1 KD conditioned media transcriptionally reprogrammed parental HCC cells activated regulatory CD4+/CD25+/FoxP3+ T cells (Tregs). Conclusions: Loss of macroH2A1 in HCC cells drives cancer stem-cell propagation and evasion from immune surveillance

Role of heme oxygenase-1 (HSP32) and HSP90 in glioblastoma

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. The current treatment regimes for glioblastoma demonstrated a low efficiency and offer a poor prognosis. Advancements in conventional treatment strategies have only yielded modest improvements in overall survival. The heat shockproteins, heme oxygenase-1 (HO-1) and Hsp90, serve these pivotal roles in tumor cells and have been identified as effective targets for developing therapeutics. This topic review summarizes the current preclinical and clinical evidences and rationale to define the potential of HO-1 and Hsp90 in GBM progression and chemoresistance

INFLAMMATORY BOWEL DISEASE AND PERIPHERAL ATRHITIS: MESALAZINA AND PROBIOTICS

The inflammaotory bowel disease (IBD) are a group of inflammatory pathologies of the digestive line with chronicity and recurrent characteristic. The IBDs mostly recognized are the ulcerative colitis and Crohn's disease; they are more frequent in the industrialized countries and among the caucasian populations that among those africans or oriental. The secondary artropaties to IBD recognize a multifactorial genesis in subjects predisposed as a result genetically or environmental factors; a fundamental role of the intestinal dysbiosis they are hypothesized

Extracellular Superoxide Dismutase Expression in Papillary Thyroid Cancer Mesenchymal Stem/Stromal Cells Modulates Cancer Cell Growth and Migration

Tumor stroma-secreted growth factors, cytokines, and reactive oxygen species (ROS) influence tumor development from early stages to the metastasis phase. Previous studies have demonstrated downregulation of ROS-producing extracellular superoxide dismutase (SOD3) in thyroid cancer cell lines although according to recent data, the expression of SOD3 at physiological levels stimulates normal and cancer cell proliferation. Therefore, to analyze the expression of SOD3 in tumor stroma, we characterized stromal cells from the thyroid. We report mutually exclusive desmoplasia and inflammation in papillary and follicular thyroid cancers and the presence of multipotent mesenchymal stem/stromal cells (MSCs) in non-carcinogenic thyroids and papillary thyroid cancer (PTC). The phenotypic and differentiation characteristics of Thyroid MSCs and PTC MSCs were comparable with bone marrow MSCs. A molecular level analysis showed increased FIBROBLAST ACTIVATING PROTEIN, COLLAGEN 1 TYPE A1, TENASCIN, and SOD3 expression in PTC MSCs compared to Thyroid MSCs, suggesting the presence of MSCs with a fibrotic fingerprint in papillary thyroid cancer tumors and the autocrine-paracrine conversion of SOD3 expression, which was enhanced by cancer cells. Stromal SOD3 had a stimulatory effect on cancer cell growth and an inhibitory effect on cancer cell migration, thus indicating that SOD3 might be a novel player in thyroid tumor stroma

Probiotics as Potential Therapeutic Agents: Safeguarding Skeletal Muscle against Alcohol-Induced Damage through the Gut–Liver–Muscle Axis

Probiotics have shown the potential to counteract the loss of muscle mass, reduce physical fatigue, and mitigate inflammatory response following intense exercise, although the mechanisms by which they work are not very clear. The objective of this review is to describe the main harmful effects of alcohol on skeletal muscle and to provide important strategies based on the use of probiotics. The excessive consumption of alcohol is a worldwide problem and has been shown to be crucial in the progression of alcoholic liver disease (ALD), for which, to date, the only therapy available is lifestyle modification, including cessation of drinking. In ALD, alcohol contributes significantly to the loss of skeletal muscle, and also to changes in the intestinal microbiota, which are the basis for a series of problems related to the onset of sarcopenia. Some of the main effects of alcohol on the skeletal muscle are described in this review, with particular emphasis on the “gut-liver-muscle axis”, which seems to be the primary cause of a series of muscle dysfunctions related to the onset of ALD. The modulation of the intestinal microbiota through probiotics utilization has appeared to be crucial in mitigating the muscle damage induced by the high amounts of alcohol consumed

INFLAMMATORY BOWEL DISEASE AND COLORECTAL CANCER, NUTRACEUTICAL ASPECTS

Nutraceuticals constitute a group of functional foods that provide added health benefits for various disorders including inflammatory bowel disease (IBD) and colorectal cancer (CCR). The main groups of nutraceuticals include probiotics, prebiotics omega 3 and antioxidants. Studies on nutraceutical showed that this type of food possessed similar properties to drugs but with the benefit of not having side effects. This mini review shows that probiotics and prebiotics, when administered simultaneously with traditional therapies, reduce IBD symptoms and reduce synthesis of enzymes probably involved in colorectal carcinogenesis. Moreover, Omega 3 reduces the synthesis of inflammation mediators and prevenents carcinogenesis through interaction interaction with the signaling pathway NOTCH1/MMP9. Moreover, antioxidant reduce the inflammatory process by inhibiting the synthesis of inflammatory mediators, and inhibit the mechanisms of cell proliferation by inducing apoptosis. In brief, nutraceuticals have gained a huge clinical interest since they could be used along with traditional therapy. Bioavailability studies of nutracetical supplements guarantee a correct intake of the substance by oral administration, a matter which would not have been posible to have entirely with the consumprtion of regular food only

Post-mortem findings in vaccine-induced thrombotic thombocytopenia

Greinacher et al.1 and Schultz et al.2 were the first to independently report the main clinical and laboratory features of 11 and five respective patients from Germany, Austria and Norway who developed life-threatening thrombohemorrhagic complications 5 to 16 days after the administration of the first dose of the chimpanzee adenoviral vector vaccine ChAdOx1nCoV-19 against SARS-CoV-2 and COVID-19. Subsequently Scully et al.3 reported similar findings in 23 patients treated with the same vaccine in the United Kingdom. More recently, See et al.4 reported a case series of 12 patients from the USA with cerebral venous sinus thrombosis following the vaccination with Ad26.CoV2.S employing a human adenoviral vector. The main post-vaccination features common to the case series were the occurrence of venous thromboembolism mainly in unusual sites (cerebral and abdominal veins) and the concomitant presence of bleeding symptoms associated with severe thrombocytopenia, often accompanied by laboratory signs of consumption coagulopathy with low plasma fibrinogen and hugely increased levels of D-dimer. The majority of reported patients reacted positively for serum immunoglobulin G (IgG) antibodies to the platelet factor 4 PF4/heparin complex. 1-4 Another common feature was the high mortality rate. The mechanism of this very rare thrombohemorrhagic syndrome was postulated to be a vaccine-triggered autoimmune reaction, with the development of antibodies against a still ill-defined PF4/polyanion complex that causes platelet activation as in heparin-induced thrombocytopenia (HIT),1-4 notwithstanding the fact that no cases were exposed to heparin before the onset of thrombosis and thrombocytopenia. We report herewith the detailed post-mortem macroscopic and microscopic findings in two similar cases that occurred in the Italian region of Sicily

COLORECTAL CARCINOGENESIS; ROLE OF OXIDATIVE STRESS AND ANTIOXIDANTS

One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanism. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documentes the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yeld definitive results and were performed mostly in vitro on cell population, or in vivo in experimental animal models

PRENATAL DEVELOPMENT OF TEMPORO-MANDIBULAR JOINTS: STATE OF ART

The aim of this work is to analyze the state of the art of temporo-mandibular joint (MJ) to understand the varoius stage of the development of the same during embryogenesis. Various theories have been analyzed, such as the formation of apoptotic or the important role of growth factors, or the Valencia et studies in which are analyzed to numerous articular diseases in various stage of development. By the aforementioned studies show that many factors, of a different nature, are to be involved in the prenatal developlment of this important joint