Hyperhomocysteinemia is recognized as a risk factor for several diseases, including cardiovascular and neurological conditions. Homocysteine (HCys) is a key metabolite involved in the biosynthesis and metabolism of methionine (Met), which plays a pivotal role in the physiological cell's life cycle. The biochemistry of Met is finely regulated by several enzymes that control HCys concentration. Indeed, balanced activity among the enzymes is essential for the cell's well-being, while its malfunction could raise HCys concentration which can lead to the onset of several pathological conditions. The HCys concentration increase seems to be caused mainly by the widely diffused polymorphisms of several enzymes. Nowadays, a blood test can easily detect elevated concentrations of HCys, referred to as Hyperhomocysteinemia (HHCys). Prolonged exposure to this condition can lead to the onset of cardiovascular disease and can lead to the development of atherosclerosis, stroke, inflammatory syndromes like osteoporosis and rheumatism, as well as neuronal pathologies including Alzheimer's and Parkinson's diseases. In this review, we analyzed the literature of several pathological conditions in which the molecular pathways of HHCys are involved. Interestingly, several observations indicate that the calibrated assumption of correct doses of vitamins such as folic acid, vitamin B6, vitamin B12, and betaine may control HHCys-related conditions.

Platinum-based agents, such as cisplatin, form the mainstay of currently used chemotherapeutic regimens for several malignancies; however, the main limitations are chemoresistance and ototoxic side effects. In this study we used two different polyphenols, curcumin and ferulic acid as adjuvant chemotherapeutics evaluating (1) in vivo their antioxidant effects in protecting against cisplatin ototoxicity and (2) in vitro the transcription factors involved in tumor progression and cisplatin resistance. We reported that both polyphenols show antioxidant and oto-protective activity in the cochlea by up-regulating Nrf-2/HO-1 pathway and downregulating p53 phosphorylation. However, only curcumin is able to influence inflammatory pathways counteracting NF-κB activation. In human cancer cells, curcumin converts the anti-oxidant effect into a pro-oxidant and anti-inflammatory one. Curcumin exerts permissive and chemosensitive properties by targeting the cisplatin chemoresistant factors Nrf-2, NF-κB and STAT-3 phosphorylation. Ferulic acid shows a biphasic response: it is pro-oxidant at lower concentrations and anti-oxidant at higher concentrations promoting chemoresistance. Thus, polyphenols, mainly curcumin, targeting ROS-modulated pathways may be a promising tool for cancer therapy. Thanks to their biphasic activity of antioxidant in normal cells undergoing stressful conditions and pro-oxidant in cancer cells, these polyphenols probably engage an interplay among the key factors Nrf-2, NF-κB, STAT-3 and p53. Cisplatin chemotherapy has been a mainstay of cancer treatment 1. In general, cisplatin is considered a cytotoxic drug which kills cancer cells by the formation of intra-and inter-strand DNA crosslinks as well as cisplatin DNA adducts 2-4. The molecular mechanisms of action are complex and involve multiple events that include induction of oxidative stress as characterized by reactive oxygen species (ROS) production and lipid peroxidation, inflammation by activating pro-inflammatory factors, induction of p53-dependent signaling pathways 5. However, cisplatin chemotherapy is also associated with substantial side effects that include ototoxic damage 6-9. Elevation of hearing threshold, mainly for the higher frequencies, has been reported in 22 to 75% of adult patients 10 and 26 to 90% of pediatric patients 11 ; it results in significant and permanent hearing loss that is especially debilitating in young children 11. A growing body of research is dedicated to elucidate the molecular mechanisms implicated in cisplatin toxicity and resistance, including oxidative stress and inflammation 4,12-15. Still, the molecular mechanisms underlying the enhanced sensitivity or resistance to cisplatin-induced apoptosis and cisplatin adverse effects are poorly understood. In the present research we considered that combination therapies of cisplatin with other drugs have become challenging in the treatment of human cancers to overcome drug resistance and reduce the undesirable side effects. Currently, natural products or nutraceuticals are...

The outbreak of the COVID-19 pandemic has led to a disruption of surgical care. The aim of this multi-centric, retrospective study was to evaluate the impact of the pandemic on surgical activity for thyroid disease among the Italian Units of Endocrine Surgery. Three phases of the pandemic were identified based on the epidemiological situation and the public measures adopted from the Italian Government (1st phase: from 9th March to 3rd May 2020; 2nd phase: from 4th May to 14th June; 3rd phase: from 15th June to 31st). The patients operated upon during these phases were compared to those who underwent surgery during the same period of the previous year. Overall, 3892 patients from 28 Italian endocrine surgical units were included in the study, 1478 (38%) operated upon during COVID-19 pandemic, and 2414 (62%) during the corresponding period of 2019. The decrease in the number of operations was by 64.8%, 44.7% and 5.1% during the three phases of COVID-19 pandemic, compared to 2019, respectively. During the first and the second phases, the surgical activity was dedicated mainly to oncological patients. No differences in post-operative complications were noted between the two periods. Oncological activity for thyroid cancer was adequately maintained during the COVID-19 pandemic.

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The effectiveness of RA given via trans-tympanic injection could be interesting for the future application of this minimally-invasive procedure in the treatment of ROS-induced hearing loss.

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The aim of this paper is to discuss the risk of recurrence in patients with differentiated thyroid cancer and emphasize the importance of risk-group stratification, early recurrence identification and application of new imaging modalities, what is the PET-CT. Moreover, follow-up of patients with thyroid carcinoma should be carried out by specialized teams throughout life. Therefore, interdisciplinary case discussions in tumor conferences may improve the use of multimodal therapy especially in patients with poorly differentiated thyroid carcinomas. After baseline follow-up, if there is a suspicion of thyroid carcinoma, early PET-CT should be used for early detection and appropriate planning. Fortunately, due to the good localization possibility, the PET-CT enables a focused surgical procedure with avoidance of an unnecessary tumor search and thereby a reduction of the risk of injury of neighboring structures which is a concern with reoperative neck surgery.