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Life (Basel, Switzerland) Jun 2024Amino acids are one of the most important building blocks of life. During the biochemical process of translation, cells sequentially connect amino acids via amide bonds...
From Zero to Hero: The Cyanide-Free Formation of Amino Acids and Amides from Acetylene, Ammonia and Carbon Monoxide in Aqueous Environments in a Simulated Hadean Scenario.
Amino acids are one of the most important building blocks of life. During the biochemical process of translation, cells sequentially connect amino acids via amide bonds to synthesize proteins, using the genetic information in messenger RNA (mRNA) as a template. From a prebiotic perspective (i.e., without enzymatic catalysis), joining amino acids to peptides via amide bonds is difficult due to the highly endergonic nature of the condensation reaction. We show here that amides can be formed in reactions catalyzed by the transition metal sulfides from acetylene, carbon monoxide and ammonia under aqueous conditions. Some α- and β-amino acids were also formed under the same conditions, demonstrating an alternative cyanide-free path for the formation of amino acids in prebiotic environments. Experiments performed with stable isotope labeled precursors, like NHCl and C-acetylene, enabled the accurate mass spectroscopic identification of the products formed from the starting materials and their composition. Reactions catalyzed using the transition metal sulfides seem to offer a promising alternative pathway for the formation of amides and amino acids in prebiotic environments, bypassing the challenges posed by the highly endergonic condensation reaction. These findings shed light on the potential mechanisms by which the building blocks of life could have originated on early Earth.
PubMed: 38929702
DOI: 10.3390/life14060719 -
Life (Basel, Switzerland) May 2024Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although... (Review)
Review
Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although it is not considered a precursor of cancer, endometriosis is associated with ovarian cancer. In this review, we summarized the evidence that clear-cell and endometrioid ovarian carcinomas (endometriosis-associated ovarian carcinoma-EAOC) may arise in endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interaction domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in phosphatidylinositol 3-kinase (PI3K) which frequently coexist. Recent studies have also suggested the simultaneous role of the tumor-suppressor gene in the early malignant transformation of endometriosis and the contribution of deficient MMR (mismatch repair) protein status in the pathogenesis of EAOC. In addition to activating and inactivating mutations in cancer driver genes, the complex pathogenesis of EAOC involves multiple other mechanisms such as the modulation of cancer driver genes via the transcriptional and post-translational (miRNA) modulation of cancer driver genes and the interplay with the inflammatory tissue microenvironment. This knowledge is being translated into the clinical management of endometriosis and EAOC. This includes the identification of the new biomarkers predictive of the risk of endometriosis and cancer, and it will shape the precision oncology treatment of EAOC.
PubMed: 38929687
DOI: 10.3390/life14060704 -
Medicina (Kaunas, Lithuania) Jun 2024The focus on mild cognitive dysfunction in adults is of great interest, given the risk of worsening and conversion to dementia. Cognitive dysfunctions are characterized... (Randomized Controlled Trial)
Randomized Controlled Trial
The focus on mild cognitive dysfunction in adults is of great interest, given the risk of worsening and conversion to dementia. Cognitive dysfunctions are characterized by a decrease in the weight and volume of the brain, due to cortical atrophy, with a widening of the grooves and flattening of the convolutions. Brain atrophy that mainly involves the hippocampus is related to the progression of cognitive impairment and the conversion from mild cognitive dysfunction to dementia. Currently, there is no treatment for MCI. Results from a trial on Alzheimer's disease (ASCOMALVA trial) suggest that a sustained cholinergic challenge can slow the progression of brain atrophy typical of Alzheimer's disease associated with vascular damage. This study intends to evaluate the efficacy of choline alphoscerate in patients with mild cognitive impairment (MCI) and associated vascular damage, in stabilizing and/or slowing brain atrophy typical of adult-onset cognitive dysfunction, and in improving and/or slowing the progression of cognitive and behavioral symptoms associated with MCI. : This randomized controlled trial will recruit 60 patients that will be evaluated and randomized in a 1:1 ratio to receive choline alphoscerate (1200 mg/day) or placebo, for 12 months. Analyses will be carried out using SPSS vesion No 26 the Statistician in charge of this study, with the statistical significance level chosen as 0.05. : This trial may provide evidence about the efficacy of treatment with the cholinergic precursor choline alphoscerate in patients with mild cognitive dysfunction. The results of this study will be published in peer-reviewed journals. EudraCT number: 2020-000576-38.
Topics: Humans; Cognitive Dysfunction; Glycerylphosphorylcholine; Male; Female; Aged; Middle Aged; Cholinergic Agents; Randomized Controlled Trials as Topic
PubMed: 38929542
DOI: 10.3390/medicina60060925 -
Medicina (Kaunas, Lithuania) May 2024: Our aim was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of...
: Our aim was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. : The study compared 404 patients who underwent cervical cone biopsy for cervical cancer. The study examined patients' specimens based on histopathological characteristics and categorized cervical lesions based on pap smear. : There was a statistically significant age difference between the two study periods. The mean difference was 32 years before the pandemic and 35 years during the pandemic (-value > 0.05). The biggest patient loss ratio identified by age group was in the 50-59-year group, with a 14.53% loss in the pre-pandemic period and a 9.1% loss in the pandemic period. In the pandemic period, patients from rural areas presented in the clinical trial with a lower rate of 39.52% (83 patients) vs. 60.47% (127 patients) in urban areas. A higher percentage of patients experiencing cervicorrhagia as a clinical manifestation in the pandemic period vs. the pre-pandemic period, with an increase in more severe lesions in the pandemic period, had a statistical significance of 8% more newly diagnosed compared to the pre-pandemic period. : The addressability of the patients during the COVID period was not affected in a drastic way in our study. We encountered a decrease in appointments in the age group of 50-59 years and a decrease in patients with rural residence. In our study, we found an increase in cervical bleeding as a reason for consultation in the pandemic period with a higher lesion degree, both on a pap smear and on a cervical biopsy.
Topics: Humans; Female; COVID-19; Retrospective Studies; Middle Aged; Uterine Cervical Neoplasms; Adult; SARS-CoV-2; Papanicolaou Test; Early Detection of Cancer; Aged; Pandemics; Vaginal Smears
PubMed: 38929526
DOI: 10.3390/medicina60060909 -
Antioxidants (Basel, Switzerland) May 2024Red light (670 nm) energy controls vasodilation via the formation of a transferable endothelium-derived nitric oxide (NO)-precursor-containing substance, its...
Red light (670 nm) energy controls vasodilation via the formation of a transferable endothelium-derived nitric oxide (NO)-precursor-containing substance, its intracellular traffic, and exocytosis. Here we investigated the underlying mechanistic effect of oxidative stress on light-mediated vasodilation by using pressure myography on dissected murine arteries and immunofluorescence on endothelial cells. Treatment with antioxidants Trolox and catalase decreased vessel dilation. In the presence of catalase, a lower number of exosomes were detected in the vessel bath. Light exposure resulted in increased cellular free radical levels. Mitochondrial reactive oxygen species were also more abundant but did not alter cellular ATP production. Red light enhanced the co-localization of late exosome marker CD63 and cellular S-nitrosoprotein to a greater extent than high glucose, suggesting that a mild oxidative stress favors the localization of NO precursor in late exosomes. Exocytosis regulating protein Rab11 was more abundant after irradiation. Our findings conclude that red-light-induced gentle oxidative stress facilitates the dilation of blood vessels, most likely through empowering the traffic of vasodilatory substances. Application of antioxidants disfavors this mechanism.
PubMed: 38929107
DOI: 10.3390/antiox13060668 -
Foods (Basel, Switzerland) Jun 2024The wide ampelographic treasure of Italian wine grape varieties is driving research towards suitable approaches for the varietal authenticity control of wine. In this...
The wide ampelographic treasure of Italian wine grape varieties is driving research towards suitable approaches for the varietal authenticity control of wine. In this paper, Aglianico, Negroamaro, Primitivo and Uva di Troia red wines, which were produced experimentally by single-grape winemaking from non-aromatic grapes native to southern Italy, were analyzed with respect to berry markers, namely anthocyanins, hydroxycinnamic acids (HPLC-DAD), shikimic acid (HPLC-UV) and glycosidic aroma precursors (GC-MS). The study confirms that, just as for the berries, useful varietal authenticity markers for red wine, even after aging, turn out to be hydroxycinnamic acids, relative amounts of acylated forms of anthocyanins, and shikimic acid, together with some grape glycosidic precursors from terpenes and C- norisoprenoids. Principal Component Analysis was used as a valuable tool to highlight the results.
PubMed: 38928808
DOI: 10.3390/foods13121866 -
International Journal of Molecular... Jun 2024Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables,...
Onion ( L.) Flavonoid Extract Ameliorates Osteoporosis in Rats Facilitating Osteoblast Proliferation and Differentiation in MG-63 Cells and Inhibiting RANKL-Induced Osteoclastogenesis in RAW 264.7 Cells.
Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables, fruits, beans, and cereals, have been reported for their anti-osteoporotic properties. Onion is a commonly consumed vegetable rich in flavonoids with diverse pharmacological activities. In this study, the trabecular structure was enhanced and bone mineral density (BMD) exhibited a twofold increase following oral administration of onion flavonoid extract (OFE). The levels of estradiol (E2), calcium (Ca), and phosphorus (P) in serum were significantly increased in ovariectomized (OVX) rats, with effects equal to alendronate sodium (ALN). Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) levels in rat serum were reduced by 35.7% and 36.9%, respectively, compared to the OVX group. In addition, the effects of OFE on bone health were assessed using human osteoblast-like cells MG-63 and osteoclast precursor RAW 264.7 cells in vitro as well. Proliferation and mineralization of MG-63 cells were promoted by OFE treatment, along with increased ALP activity and mRNA expression of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL). Additionally, RANKL-induced osteoclastogenesis and osteoclast activity were inhibited by OFE treatment through decreased TRAP activity and down-regulation of mRNA expression-related enzymes in RAW 264.7 cells. Overall findings suggest that OFE holds promise as a natural functional component for alleviating osteoporosis.
Topics: Animals; Osteoblasts; RANK Ligand; Osteoporosis; Flavonoids; Mice; Onions; Cell Differentiation; Plant Extracts; Rats; Cell Proliferation; RAW 264.7 Cells; Osteogenesis; Humans; Female; Osteoclasts; Bone Density; Ovariectomy; Rats, Sprague-Dawley; Osteoprotegerin
PubMed: 38928460
DOI: 10.3390/ijms25126754 -
International Journal of Molecular... Jun 2024Phytaspases differ from other members of the plant subtilisin-like protease family by having rare aspartate cleavage specificity and unusual localization dynamics....
Phytaspases differ from other members of the plant subtilisin-like protease family by having rare aspartate cleavage specificity and unusual localization dynamics. Phytaspases are secreted from healthy plant cells but are re-internalized upon perception of death-inducing stresses. Although proteolytic activity is required for the secretion of plant subtilases, its requirement for the retrograde transportation of phytaspases is currently unknown. To address this issue, we employed an approach to complement in trans the externalization of a prodomain-less form of phytaspase (Phyt) with the free prodomain in leaf cells. Using this approach, the generation of the proteolytically active Phyt and its transport to the extracellular space at a level comparable to that of the native Phyt (synthesized as a canonical prodomain-containing precursor protein) were achieved. The application of this methodology to Phyt with a mutated catalytic Ser537 residue resulted in the secretion of the inactive, although processed (prodomain-free), protein as well. Notably, the externalized Phyt Ser537Ala mutant was still capable of retrograde transportation into plant cells upon the induction of oxidative stress. Our data thus indicate that the proteolytic activity of Phyt is dispensable for stress-induced retrograde transport of the enzyme.
Topics: Nicotiana; Proteolysis; Plant Proteins; Oxidative Stress; Stress, Physiological; Subtilisins; Plant Leaves; Protein Transport
PubMed: 38928451
DOI: 10.3390/ijms25126729 -
International Journal of Molecular... Jun 2024Tumor cells reprogram their metabolism to meet the increased demand for nucleotides and other molecules necessary for growth and proliferation. In fact, cancer cells are... (Review)
Review
Tumor cells reprogram their metabolism to meet the increased demand for nucleotides and other molecules necessary for growth and proliferation. In fact, cancer cells are characterized by an increased "de novo" synthesis of purine nucleotides. Therefore, it is not surprising that specific enzymes of purine metabolism are the targets of drugs as antineoplastic agents, and a better knowledge of the mechanisms underlying their regulation would be of great help in finding new therapeutic approaches. The mammalian target of the rapamycin (mTOR) signaling pathway, which is often activated in cancer cells, promotes anabolic processes and is a major regulator of cell growth and division. Among the numerous effects exerted by mTOR, noteworthy is its empowerment of the "de novo" synthesis of nucleotides, accomplished by supporting the formation of purinosomes, and by increasing the availability of necessary precursors, such as one-carbon formyl group, bicarbonate and 5-phosphoribosyl-1-pyrophosphate. In this review, we highlight the connection between purine and mitochondrial metabolism, and the bidirectional relation between mTOR signaling and purine synthesis pathways.
Topics: Humans; Neoplasms; TOR Serine-Threonine Kinases; Purines; Signal Transduction; Animals; Mitochondria
PubMed: 38928439
DOI: 10.3390/ijms25126735 -
International Journal of Molecular... Jun 2024A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA...
A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation was analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors-of both primitive endocardial tubes-committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant novelty, our results revealed that miR-1 increased , and , while this microRNA diminished and expressions during early differentiation of the cardiac sinoatrial region. Furthermore, we observed in this developmental context that miR-1 upregulated and and downregulated , which are three crucial factors in the retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacted with and /, as well as with /, which are three key factors actively involved in regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in the early differentiation of the cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and , fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.
Topics: Animals; MicroRNAs; Epigenesis, Genetic; Cell Differentiation; Gene Expression Regulation, Developmental; Chick Embryo; MEF2 Transcription Factors; Sinoatrial Node; Signal Transduction; Heart
PubMed: 38928314
DOI: 10.3390/ijms25126608