1,721,020 research outputs found

    The Multifaceted Role of the Polyphenol Curcumin: A Focus on Type 2 Diabetes Mellitus

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    Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by chronic hyperglycemia, which often co-exists with other metabolic impairments. This condition can damage various tissues and organs, resulting in the development of severe complications, both microvascular, such as retinopathy, nephropathy, and neuropathy, and macrovascular, responsible for an increased risk of cardiovascular diseases. Curcumin is the main bioactive molecule found in the rhizomes of turmeric. Many studies have reported curcumin to exhibit antioxidant, anti-inflammatory, anti-infectious, and anti-cancer properties; thus, there is an increasing interest in exploiting these properties in order to prevent the rise or the progression of T2DM, as well as its possible associated conditions. In this review, we have presented the current state-ofart regarding the clinical trials that have involved curcumin administration and analyzed the possible mechanisms by which curcumin might exert the beneficial effects observed in literature

    Gaining new insights on the Hsp90 regulatory network

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    The heat shock protein Hsp90 is a molecular chaperon that uses ATP and interacts with various co-chaperone proteins, acting as adapters, in order to carry out the maturation of its target proteins. In physiological conditions, the heat shock proteins (HSPs) favour post-translational modification, protein folding and sub-cellular transport of their "client" proteins. In stress conditions, many misfolded proteins accumulate exposing their hydrophobic residues and these are recognized by HSPs which prevent the aggregation and favour the correct folding. In case this is no longer possible, HSPs mediate elimination of such misfolded proteins, mainly by ubiquitin-proteasome system

    Circulating miRNAs and Preeclampsia: From Implantation to Epigenetics

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    In this review, we comprehensively present the literature on circulating microRNAs (miRNAs) associated with preeclampsia, a pregnancy-specific disease considered the primary reason for maternal and fetal mortality and morbidity. miRNAs are single-stranded non-coding RNAs, 20-24 nt long, which control mRNA expression. Changes in miRNA expression can induce a variation in the relative mRNA level and influence cellular homeostasis, and the strong presence of miRNAs in all body fluids has made them useful biomarkers of several diseases. Preeclampsia is a multifactorial disease, but the etiopathogenesis remains unclear. The functions of trophoblasts, including differentiation, proliferation, migration, invasion and apoptosis, are essential for a successful pregnancy. During the early stages of placental development, trophoblasts are strictly regulated by several molecular pathways; however, an imbalance in these molecular pathways can lead to severe placental lesions and pregnancy complications. We then discuss the role of miRNAs in trophoblast invasion and in the pathogenesis, diagnosis and prediction of preeclampsia. We also discuss the potential role of miRNAs from an epigenetic perspective with possible future therapeutic implications

    Placental klotho protein in preeclampsia: A possible link to long term outcomes.

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    Introduction An aging-suppressor gene, klotho, is a candidate factor for vascular disease because its deficiency leads to impaired endothelium-dependent vasodilation and impaired angiogenesis. Although klotho protein is predominantly expressed in the kidney, it is detected in a limited number of other tissues, such as the placenta, ovary, prostate gland, and small intestine. This protein is involved in several metabolic pathways such as calcium and phosphate homeostasis, the insulin-like growth factor 1 (IGF-1), apoptosis, angiotensin-II-induced events in the kidney and oxidative stress. Objectives The aim was to assess the expression of the klotho gene in the placenta from pregnancies affected by severe preeclampsia. Methods Placentas were collected from normal pregnancies (n = 12) and pregnancies complicated by preeclampsia (n = 12), matched for gestational age. Klotho mRNA and protein were determined using real-time quantitative polymerase chain reaction (PCR) and Western blot, respectively. Results Real-Time PCR analyses demonstrated a significant (p = 0.005) 83% down-regulation of Klotho in patients with Preeclampsia versus Controls. Results of Western Blot agreed with those from Real-Time PCR. Conclusion Klotho mRNA expression in the placenta is decreased in preeclamptic pregnancies. Given its role in cardiovascular disease in aging, it may link preeclamptic mothers and their offsprings to long term cardiovascular outcomes

    Catecholamine O-Methyltransferase as a Promising Diagnostic and Therapeutic Target in Oral Squamous Cell Carcinoma

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    Oral squamous cell carcinoma (OSCC), which constitutes over 90% of all oral cancers, is the most prevalent malignancy affecting the oral cavity and is marked by high aggressive behavior and high recurrence rate. Although significant progress has been made in therapeutic strategies, the overall prognosis for OSCC patients remains poor, primarily due to the common occurrence of late-stage diagnosis and the frequent development of metastases. Therefore, implementing effective early detection methods alongside the development of targeted therapies is essential to significantly enhance clinical outcomes and long-term survival rates in affected individuals. In this experimental study, we focused on Catecholamine OMethyltransferase (COMT), a key enzyme involved in the metabolic breakdown of catecholamines such as dopamine, epinephrine, and norepinephrine. COMT regulates neurotransmitter levels and oxidative stress, and its polymorphisms have been linked to cancer susceptibility, progression, and therapeutic response. COMT expression levels were assessed at both mRNA and protein level in OSCC specimens compared to adjacent healthy tissue. Our findings demonstrated a significant overexpression of COMT in cancerous tissues, suggesting its potential role as a diagnostic marker. Ongoing functional analyses are being performed using gene knockdown approaches to elucidate the role of the enzyme in OSCC phenotype

    Unexplained fetal loss: the fetal side of thrombophilia.

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    Carrier status of the fetus for factor V polymorphism or double homozygosity for mutant alleles of the PAI-1 4 G/4 G and MTHFR T677 T polymorphisms must be considered risk factors for intrauterine fetal death. The clinical implications of these data need to be addressed in a prospective study to confirm our preliminary data and to answer the question of whether or not double homozygous individuals should be treated with low molecular-weight heparin and/or low-dose aspirin
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