Dissecting the Functional Role of the TRIM8 Protein on Cancer Pathogenesis.

TRIM/RBCC are a large family of proteins that include more than 80 proteins, most of which act as E3 ligases and catalyze the direct transfer of Ubiquitin, SUMO and ISG15 on specific protein substrates. They are involved in oncogenesis processes and in cellular immunity. On this topic, we focus on TRIM8 and its multiple roles in tumor pathologies. TRIM8 inhibits breast cancer proliferation through the regulation of estrogen signaling. TRIM8 downregulation in glioma is involved in cell proliferation, and it is related to patients' survival. Several studies suggested that TRIM8 regulates the p53 suppressor signaling pathway: it is involved in the NF-kB pathway (Nuclear Factor kappa light- chain-enhancer of activated B cells) and in STAT3 (Signal Transducer and Activator of Transcription 3) of the JAK-STAT pathway. In this review, we summarize how the association between these different pathways reflects a dual role of TRIM8 in cancer as an oncogene or a tumor suppressor gene.

When should cardiovascular prevention begin? The importance of antenatal, perinatal and primordial prevention.

Cardiovascular diseases represent a major health problem, being one of the leading causes of morbidity and mortality worldwide. Therefore, in this scenario, cardiovascular prevention plays an essential role although it is difficult to establish when promoting and implementing preventive strategies. However, there is growing evidence that prevention should start even before birth, during pregnancy, aiming to avoid the onset of cardiovascular risk factors, since events that occur early in life have a great impact on the cardiovascular risk profile of an adult. The two pillars of this early preventive strategy are nutrition and physical exercise, together with prevention of cardio-metabolic diseases during pregnancy. This review attempts to gather the growing evidence of the benefits of antenatal, perinatal and primordial prevention, discussing also the possibility to reverse or to mitigate the cardiovascular profile developed in the initial stages of life. This could pave the way for future research, investigating the optimal time and duration of these preventing measures, their duration and maintenance in adulthood, and the most effective interventions according to the different age and guiding in the next years, the best clinical practice and the political strategies to cope with cardiovascular disease.

The kidney, COVID-19, and the chemokine network: an intriguing trio.

On December 30th 2019, some patients with pneumonia of unknown etiology were reported in the Program for Monitoring Emerging Diseases (ProMED), a program run by the International Society for Infectious Diseases (ISID), hypothesized to be related to subjects who had had contact with the seafood market in Wuhan, China. Chinese authorities instituted an emergency agency aimed at identifying the source of infection and potential biological pathogens. It was subsequently named by the World Committee on Virus Classification as 2019-nCoV (2019-novel coronavirus) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of studies have demonstrated that 2019-nCoV and the SARS-CoV shared the same cell entry receptor named angiotensin-converting enzyme 2 (ACE2). This is expressed in human tissues, not only in the respiratory epithelia, but also in the small intestines, heart, liver, and kidneys. Here, we examine the most recent findings on the effects of SARS-CoV-2 infection on kidney diseases, mainly acute kidney injury, and the potential role of the chemokine network.

The Impact of Metabolic Syndrome and Its Components on Female Sexual Dysfunction: A Narrative Mini-Review.

BACKGROUND: The impact of metabolic syndrome on female sexual dysfunction received modest consideration in clinical practice. The aim of the research was to analyze the international literature to determine the relationship between the metabolic syndrome, its components and female sexual disorders. METHODS: We identified relevant full-length papers by electronic databases as Index Medicus/Medline, Scopus, Life Science Journals, from 2005 to the present. Studies were searched using the following as search query: metabolic syndrome, female sexual dysfunction, obesity, systemic arterial hypertension, diabetes mellitus, dyslipidemia. RESULTS: Women with metabolic syndrome showed higher prevalence of sexual inactivity and low sexual desire, orgasm and satisfaction respect to women without metabolic syndrome. Particularly metabolic components as diabetes mellitus, dy-slipidemia, systemic arterial hypertension were strongly associated with lower sexual desire, activity and Female Sexual Function Index total score. In contrast, other studies showed no relationship. CONCLUSION: Our study showed that in the clinical evaluation of women with metabolic syndrome routine inquiring about female sexual dysfunction should be recommended to ameliorate sexual function and quality of life. However more prospective and longitudinal studies on the sexual effects of metabolic syndrome should also be suggested to know the factors related to women's sexuality better.

Metabolic Alterations, Aggressive Hormone-Naïve Prostate Cancer and Cardiovascular Disease: A Complex Relationship.

Background: Epidemiological studies suggest a possible relationship between metabolic alterations, cardiovascular disease and aggressive prostate cancer, however, no clear consensus has been reached. Objective: The aim of the study was to analyze the recent literature and summarize our experience on the association between metabolic disorders, aggressive hormone-naïve prostate cancer and cardiovascular disease. Method: We identified relevant papers by searching in electronic databases such as Scopus, Life Science Journals, and Index Medicus/Medline. Moreover, we showed our experience on the reciprocal relationship between metabolic alterations and aggressive prostate cancer, without the influence of hormone therapy, as well the role of coronary and carotid vasculopathy in advanced prostate carcinoma. Results: Prostate cancer cells have an altered metabolic homeostatic control linked to an increased aggressivity and cancer mortality. The absence of discrimination of risk factors as obesity, systemic arterial hypertension, diabetes mellitus, dyslipidemia and inaccurate selection of vascular diseases as coronary and carotid damage at initial diagnosis of prostate cancer could explain the opposite results in the literature. Systemic inflammation and oxidative stress associated with metabolic alterations and cardiovascular disease can also contribute to prostate cancer progression and increased tumor aggressivity. Conclusions: Metabolic alterations and cardiovascular disease influence aggressive and metastatic prostate cancer. Therefore, a careful evaluation of obesity, diabetes mellitus, dyslipidemia, systemic arterial hypertension, together with a careful evaluation of cardiovascular status, in particular coronary and carotid vascular disease, should be carried out after an initial diagnosis of prostatic carcinoma.

Mediterranean diet impact on cardiovascular diseases: a narrative review.

: Cardiovascular disease (CVD) accounts for more than 17 million deaths per year worldwide. It has been estimated that the influence of lifestyle on CVD mortality amounts to 13.7% for smoking, 13.2% for poor diet, and 12% for inactive lifestyle. These results deeply impact both the healthy status of individuals and their skills in working. The impact of CVD on productivity loss accounts for the 24% in total costs for CVD management.Mediterranean diet (MedD) can positively impact on natural history of CVD. It is characterized by a relatively high consumption of inexpensive and genuine food such as cereals, vegetables, legumes, nuts, fish, fresh fruits, and olive oil as the principal source of fat, low meat consumption and low-to-moderate consumption of milk, dairy products, and wine.Its effects on cardiovascular health are related to the significant improvements in arterial stiffness. Peripheral artery disease, coronary artery disease, and chronic heart failure are all positively influenced by the MedD. Furthermore, MedD lowers the risk of sudden cardiac death due to arrhythmias.The present narrative review aims to analyze the effects of MedD on CVD.

Mediterranean diet and erectile dysfunction: a current perspective.

INTRODUCTION: In this current perspective we analyzed the role of Mediterranean diet (MedDiet) in sexual function and particularly in erectile dysfunction (ED), according to the latest scientific evidence. MATERIAL AND METHODS: We conducted a systematic search of relevant full-length papers identified during the time period from 1 January 2010 to the present. RESULTS: Published studies showed that adherence to a MedDiet contributes to preventing ED through an improved lipid and glucose metabolism, increased antioxidant defenses, and increased arginine levels which could raise nitric oxide activity. CONCLUSIONS: Our findings suggest that the encouragement of a healthy lifestyle, such as MedDiet promotion, could be an attractive dietary approach to prevent ED and preserve sexual function.

Metabolic Syndrome and Aggressive Prostate Cancer at Initial Diagnosis.

Links between metabolic syndrome and prostate cancer after androgen deprivation therapy are emerging. The aim of the research was to investigate the association of metabolic syndrome and aggressive prostate malignancy, at initial diagnosis, without the influence of hormonal treatment. Retrospective analysis of 133 patients with prostate tumor diagnosis between 2007 and 2009 was conducted. Patients with prostate cancer were subdivided in 2 groups according to Gleason score: Gleason score≥7 as high-grade prostate tumor (Group 1) and <7 (Group 2) as low-grade prostate tumor. Metabolic syndrome was defined according to International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute definition. Metabolic syndrome was significantly associated with aggressive prostate cancer (OR 1.87, p<0.05) and a reduced risk of low-grade prostate cancer (OR 0.53, p<0.05) at initial diagnosis, without the influence of endocrine therapy. In our study, patients with metabolic syndrome were more likely to present with more aggressive prostate carcinoma vs. patients without metabolic syndrome. Further research should elucidate these relations in larger samples to confirm these associations and to stabilize future prevention and therapeutic strategies.

Parietal cortex integrates contextual and saliency signals during the encoding of natural scenes in working memory.

The Brief presentation of a complex scene entails that only a few objects can be selected, processed indepth, and stored in memory. Both low-level sensory salience and high-level context-related factors (e.g., the conceptual match/mismatch between objects and scene context) contribute to this selection process, but how the interplay between these factors affects memory encoding is largely unexplored. Here, during fMRI we presented participants with pictures of everyday scenes. After a short retention interval, participants judged the position of a target object extracted from the initial scene. The target object could be either congruent or incongruent with the context of the scene, and could be located in a region of the image with maximal or minimal salience. Behaviourally, we found a reduced impact of saliency on visuospatial working memory performance when the target was out-of-context. Encoding-related fMRI results showed that context-congruent targets activated dorsoparietal regions, while context-incongruent targets de-activated the ventroparietal cortex. Saliency modulated activity both in dorsal and ventral regions, with larger context-related effects for salient targets. These findings demonstrate the joint contribution of knowledge-based and saliency-driven attention for memory encoding, highlighting a dissociation between dorsal and ventral parietal regions.

Obesity, diabetes and aggressive prostate cancer hormone-naïve at initial diagnosis.

INTRODUCTION: Epidemiologic studies have implicated obesity in prostate cancer (PCa) development and aggressiveness; nevertheless, no clear consensus has been reached. The aim of the research was to investigate the association of obesity with PCa, hormone-naïve at initial diagnosis. METHODS: A retrospective analysis of 266 patients undergoing prostate biopsy at our institution, between 2006 and 2009, was conducted. We examined obesity and PCa association in 133 patients with PCa, hormone-naïve at initial diagnosis, versus 133 age-matched controls. Men with incomplete data available, a history of hormone therapy or chemotherapy, prostate or bladder surgery were excluded. RESULTS: Obesity was significantly associated (OR 2.25) with aggressive PCa (Gleason score ≥7) and inversely related (OR 0.35) to non-aggressive PCa (Gleason score ≤6). Particularly, obesity in diabetic patients was significantly linked with aggressive PCa (OR 4.17). No association was noted between obesity and PCa development. CONCLUSIONS: In our study, obese patients, particularly in combination with diabetes mellitus (DM), were more likely to present with more aggressive PCa. Further research with larger samples should be done to confirm these associations and to stabilize future prevention strategies.

[Bone metabolism, renal function and immune structure in prostate cancer. Our experience]. / Metabolismo osseo, funzionalità renale e assetto immunitario nel cancro della prostata. Nostra esperienza.

Relation studies between bone and immune system converge in recent years in osteoimmunology chapter. It has been suggested that prostate cancer cells may alter bone homeostasis, renal function and the immune system. The aim of this paper is to evaluate bone metabolism, renal function and immune process in prostate cancer patients versus control. Patients with prostate malignancy and bone metastases showed a condition of hypocalcemia and hypophosphatemia associated with increased bone anabolism and lymphopenia, suggesting a possible correlation between bone metabolism and immune context in prostate cancer.

Reciprocal cross-talk between Prostaglandin E2 and bone in prostate cancer: a current review.

In this review we analyzed the role of PGE2 as a possible regulator of bone metabolism and bone metastases in prostate cancer. Published studies were identified by searching computerized bibliographic systems from January 1(st), 2000 to July 1(st), 2011. PGE2 represents a key factor in the modulation of bone metabolism and bone metastatic disease in prostate cancer interacting with bone regulatory signals including the RANK/RANKL/OPG system and Wnt pathways. A high concentration of PGE2 exerts a prevalent stimulatory effect on osteoclastogenesis via OPG/RANK/RANKL axis activation and a inhibitory effect on osteoblastogenesis trough inhibition of Wnt pathway. An inversely low level of PGE2 exerts a stimulatory effect on osteoblastogenesis via activation of the Wnt pathway. Our finding suggests that PGE2 acts as a regulator in maintaining normal bone mass and indicate a mechanism whereby chemical manipulation of PGE2 levels or signaling may be therapeutically beneficial for prostate cancer treatment.

Chronic hypoxia, physical exercise and PSA: correlation during high-altitude trekking (2004 K2 expedition).

The aim of the present study was to identify the effects of physical exercise on PSA serum levels and the diagnostic validity of PSA in the screening of prostate cancer in subjects undergoing physical exercise during chronic hypoxia. The study was performed during trekking between 3,200 and 5,600 meters of altitude on K2 mountain for 26 days. Mean serum PSA values before and after exposure did not show significant difference due to physical exercise. These data indicate that physical exercise or mountain hypoxia do not affect the diagnostic validity of PSA.