Project description:Affiliative social motivation and behavior, that is, sociability that includes attachment, prosocial behavior (sharing, caring and helping) and empathy (the ability to understand and share the feelings of others), has high variability in the human population, with a portion of people outside of the normal range. While psychiatric disorders and autism spectrum disorders are typically associated with a deficit in social behavior, the opposite trait of hypersociability and indiscriminate friendliness are exhibited by individual with specific neurodevelopmental disorders and following early adverse care. Here we discuss both genetic and environmental factors that cause or increase the risk for developing pathological hypersociability from human to rodent models.
Project description:Breast cancer prevention is a major challenge worldwide. During the last few years, efforts have been made to identify molecular breast tissue factors that could be linked to an increased risk of developing the disease in healthy women. In this concern, steroid hormones and their receptors are key players since they are deeply involved in the growth, development and lifetime changes of the mammary gland and play a crucial role in breast cancer development and progression. In particular, androgens, by binding their own receptor, seem to exert a dichotomous effect, as they reduce cell proliferation in estrogen receptor α positive (ERα+) breast cancers while promoting tumour growth in the ERα negative ones. Despite this intricate role in cancer, very little is known about the impact of androgen receptor (AR)-mediated signalling on normal breast tissue and its correlation to breast cancer risk factors. Through an accurate collection of experimental and epidemiological studies, this review aims to elucidate whether androgens might influence the susceptibility for breast cancer. Moreover, the possibility to exploit the AR as a useful marker to predict the disease will be also evaluated.
Project description:BackgroundTrousseau syndrome (TS) refers to spontaneous, recurrent, and wandering arterial and venous thromboembolic events in patients with tumors. It results from abnormalities in coagulation and fibrinolytic mechanisms of varying degrees throughout the course of the disease. It has a high fatality rate, and it is commonly seen in patients with highly invasive tumors, such as lung, pancreatic, gastrointestinal, and breast cancers; however, to date, there has been no report of TS combined with chordoma.Case descriptionA 56-year-old male with a diagnosis of chordoma underwent surgery, immunotherapy, immunotherapy combined with antiangiogenic therapy, chemotherapy combined with immunotherapy, and proton therapy for localized metastases. Subsequent to the worsening of chest tightness, a repeat chest computed tomography angiography (CTA) scan suggested pulmonary artery embolisms; eventually, a diagnosis of TS was made. After anticoagulation and synchronized antitumor therapy, the patient's condition remained recurrent, eventually leading to death.ConclusionsTS is a frequent but easily overlooked clinical complication that can occur in a variety of tumors, including chordoma, and is currently diagnosed clinically. Thus, further exploration of its sensitive markers is needed. We have reported a case of chordoma combined with TS and conducted a literature review on TS to increase clinicians' awareness of tumor-related thromboembolism and explore strategies to optimize the diagnosis, treatment, and prevention of TS.
Project description:Ergot, fungal genus Claviceps, are worldwide distributed grass pathogens known for their production of toxic ergot alkaloids (EAs) and the great agricultural impact they have on both cereal crop and farm animal production. EAs are traditionally considered as the only factor responsible for ergot toxicity. Using broad sampling covering 13 ergot species infecting wild or agricultural grasses (including cereals) across Europe, USA, New Zealand, and South Africa we showed that the content of ergochrome pigments were comparable to the content of EAs in sclerotia. While secalonic acids A-C (SAs), the main ergot ergochromes (ECs), are well known toxins, our study is the first to address the question about their contribution to overall ergot toxicity. Based on our and published data, the importance of SAs in acute intoxication seems to be negligible, but the effect of chronic exposure needs to be evaluated. Nevertheless, they have biological activities at doses corresponding to quantities found in natural conditions. Our study highlights the need for a re-evaluation of ergot toxicity mechanisms and further studies of SAs' impact on livestock production and food safety.
Project description:The public and environmental health consequences of mercury (Hg) methylation have drawn much attention and considerable research to Hg methylation processes and their dynamics in diverse environments and under a multitude of conditions. However, the net methylmercury (MeHg) concentration that accumulates in the environment is equally determined by the rate of MeHg degradation, a complex process mediated by a variety of biotic and abiotic mechanisms, about which our knowledge is limited. Here we review the current knowledge on MeHg degradation and its potential pathways and mechanisms. We describe detoxification by resistant microorganisms that employ the Hg resistance (mer) system to reductively break the carbon-mercury (C-Hg) bond producing methane (CH4) and inorganic mercuric Hg(II), which is then reduced by the mercuric reductase to elemental Hg(0). Very recent research has begun to elucidate a mechanism for the long-recognized mer-independent oxidative demethylation, likely involving some strains of anaerobic bacteria as well as aerobic methane-oxidizing bacteria, i.e., methanotrophs. In addition, photochemical and chemical demethylation processes are described, including the roles of dissolved organic matter (DOM) and free radicals as well as dark abiotic demethylation in the natural environment about which little is currently known. We focus on mechanisms and processes of demethylation and highlight the uncertainties and known effects of environmental factors leading to MeHg degradation. Finally, we suggest future research directions to further elucidate the chemical and biochemical mechanisms of biotic and abiotic demethylation and their significance in controlling net MeHg production in natural ecosystems.
Project description:The very existence of extracellular phosphorylation has been questioned for a long time, although casein phosphorylation was discovered a century ago. In addition, several modification sites localized on secreted proteins or on extracellular or lumenal domains of transmembrane proteins have been catalogued in large scale phosphorylation analyses, though in most such studies this aspect of cellular localization was not considered. Our review presents examples when additional analyses were performed on already public data sets that revealed a wealth of information about this "neglected side" of the modification. We also sum up accumulated knowledge about extracellular phosphorylation, including the discovery of Golgi-residing kinases and the special difficulties encountered in targeted analyses. We hope future phosphorylation studies will not ignore the existence of phosphorylation outside of the cell, and further discoveries will shed more light on its biological role.
Project description:IntroductionThe optimal secondary thromboprophylactic strategies for patients with antiphospholipid syndrome (APS) and arterial thrombosis remain controversial. This study aimed to evaluate the comparative efficacy and safety of various antithrombotic strategies in APS with arterial thrombosis.MethodsA comprehensive literature search was conducted using OVID MEDLINE, EMBASE, Web of Science, and the Cochrane Controlled Register of Trials (CENTRAL) from inception until 30 September 2022, with no language restrictions. The inclusion criteria for eligible studies were as follows: inclusion of APS patients with arterial thrombosis, treatment with either antiplatelet agents, warfarin, direct oral anticoagulants (DOACs), or a combination of these therapies, and reporting of recurrent thrombotic events.ResultsWe conducted a frequentist random-effects network meta-analysis (NMA) involving 13 studies with a total of 719 participants, comprising six randomized and seven non-randomized studies. In comparison to single antiplatelet therapy (SAPT), the combined use of antiplatelet and warfarin demonstrated a significant reduction in the risk of recurrent overall thrombosis, with a risk ratio (RR) of 0.41 (95% CI 0.20 to 0.85). Dual antiplatelet therapy (DAPT) showed a lower risk of recurrent arterial thrombosis compared to SAPT although the difference did not reach statistical significance, with an RR of 0.29 (95% CI 0.08 to 1.07). DOAC was associated with a significant increase in the risk of recurrent arterial thrombosis, with an RR of 4.06 (95% CI 1.33 to 12.40) when compared to SAPT. There was no significant difference in major bleeding among various antithrombotic strategies.DiscussionBased on this NMA, the combination of warfarin and antiplatelet therapy appears to be an effective approach in preventing recurrent overall thrombosis in APS patients with a history of arterial thrombosis. While DAPT may also show promise in preventing recurrent arterial thrombosis, further studies are needed to confirm its efficacy. Conversely, the use of DOACs was found to significantly increase the risk of recurrent arterial thrombosis.