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1.
Curr Issues Mol Biol ; 46(2): 1237-1258, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38392197

RESUMO

In recent years, the nexus between genetics and biomechanics has garnered significant attention, elucidating the role of genomic determinants in shaping the biomechanical attributes of human joints, specifically the knee. This review seeks to provide a comprehensive exploration of the molecular basis underlying knee joint locomotor function. Leveraging advancements in genomic sequencing, we identified specific genetic markers and polymorphisms tied to key biomechanical features of the knee, such as ligament elasticity, meniscal resilience, and cartilage health. Particular attention was devoted to collagen genes like COL1A1 and COL5A1 and their influence on ligamentous strength and injury susceptibility. We further investigated the genetic underpinnings of knee osteoarthritis onset and progression, as well as the potential for personalized rehabilitation strategies tailored to an individual's genetic profile. We reviewed the impact of genetic factors on knee biomechanics and highlighted the importance of personalized orthopedic interventions. The results hold significant implications for injury prevention, treatment optimization, and the future of regenerative medicine, targeting not only knee joint health but joint health in general.

2.
Medicina (Kaunas) ; 60(2)2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38399589

RESUMO

This study conducts an in-depth analysis of the management of a complex arteriovenous malformation (AVM) in a 44-year-old individual, who initially manifested with acute left hemiparesis and progressively declined into a comatose state. Diagnostic neuroimaging identified a substantial right fronto-temporal intraparenchymal hematoma via a CT scan. Cerebral angiography further elucidated a choroidal AVM originating from the anterior choroidal artery, accompanied by intranidal aneurysms. The elected treatment strategy was the surgical excision of the AVM. The procedure achieved complete removal of the intracranial AVM, situated in a neurologically sensitive region, leading to notable neurological recovery. This study thoroughly explores and critically evaluates a wide spectrum of treatment approaches for intracranial arteriovenous malformations, including novel endovascular therapies. Despite extensive discourse on AVM in contemporary literature, this report is among the few documenting the treatment of a choroidal AVM via a microsurgical technique, and highlights various therapeutic options.


Assuntos
Embolização Terapêutica , Aneurisma Intracraniano , Malformações Arteriovenosas Intracranianas , Humanos , Adulto , Malformações Arteriovenosas Intracranianas/diagnóstico , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Angiografia Cerebral , Tomografia Computadorizada por Raios X
3.
Curr Issues Mol Biol ; 45(12): 9549-9565, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38132443

RESUMO

Colorectal cancer (CRC) represents the second deadliest malignancy worldwide. Around 75% of CRC patients exhibit high levels of chromosome instability that result in the accumulation of somatic copy number alterations. These alterations are associated with the amplification of oncogenes and deletion of tumor-ppressor genes and contribute to the tumoral phenotype in different malignancies. Even though this relationship is well known, much remains to be investigated regarding the effect of said alterations in long non-coding RNAs (lncRNAs) and, in turn, the impact these alterations have on the tumor phenotype. The present study aimed to evaluate the role of differentially expressed lncRNAs coded in regions with copy number alterations in colorectal cancer patient samples. We downloaded RNA-seq files of the Colorectal Adenocarcinoma Project from the The Cancer Genome Atlas (TCGA) repository (285 sequenced tumor tissues and 41 non-tumor tissues), evaluated differential expression, and mapped them over genome sequencing data with regions presenting copy number alterations. We obtained 78 differentially expressed (LFC > 1|< -1, padj < 0.05) lncRNAs, 410 miRNAs, and 5028 mRNAs and constructed a competing endogenous RNA (ceRNA) network, predicting significant lncRNA-miRNA-mRNA interactions. Said network consisted of 30 lncRNAs, 19 miRNAs, and 77 mRNAs. To understand the role that our ceRNA network played, we performed KEGG and GO analysis and found several oncogenic and anti-oncogenic processes enriched by the molecular players in our network. Finally, to evaluate the clinical relevance of the lncRNA expression, we performed survival analysis and found that C5orf64, HOTAIR, and RRN3P3 correlated with overall patient survival. Our results showed that lncRNAs coded in regions affected by SCNAs form a complex gene regulatory network in CCR.

4.
Hematol Oncol ; 41(3): 434-441, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36222822

RESUMO

2-[18 F]-FDG PET/CT is a useful diagnostic technique to assess bone and soft tissue disease in multiple myeloma (MM) but is not recommended by the International Myeloma Working Group for the evaluation of monoclonal gammopathy of undetermined significance (MGUS). The objective of this study was to evaluate the role of 2-[18 F]-FDG PET/CT in the management of these patients. An observational retrospective study was conducted on 338 patients with MGUS who underwent 2-[18 F]-FDG PET/CT. The mean age was 70.80 ± 11.84 years, and 69.2% of patients had cardiovascular risk factors. Patients were classified according to their progression risk (Mayo Clinic). The mean post-diagnosis follow-up was 8.35 ± 14.46 months. Pathological findings were recorded in 49 patients: 30 with myeloma bone lesions (15 in the initial study and 15 in follow-up) and 19 with other neoplastic (n = 13) or pathologically significant findings (n = 6). Body mass index, monoclonal component rate (MCR) > 1 g/dL and ≥1 risk factors for MM were significant in univariate logistic regression analyses. The MCR emerged as the main predictor of a positive 2-[18 F]-FDG PET/CT in adjusted multivariate regression analysis, with an area under the receiver operating characteristic curve of 0.785 and cutoff for optimal sensitivity/specificity of 1.0 ng/mL (71.4% sensitivity, 71.2% specificity). 2-[18 F]-FDG PET/CT results correctly classify patients with MGUS and could improve the detection of bone lesions over existing techniques, with the additional possibility of detecting neoplastic processes. The best parameter to predict a positive 2-[18 F]-FDG PET/CT was the MCR.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Mieloma Múltiplo/patologia , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico por imagem , Estudos Retrospectivos , Compostos Radiofarmacêuticos
5.
Int J Mol Sci ; 24(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37445986

RESUMO

Neurodegenerative diseases are, according to recent studies, one of the main causes of disability and death worldwide. Interest in molecular genetics has started to experience exponential growth thanks to numerous advancements in technology, shifts in the understanding of the disease as a phenomenon, and the change in the perspective regarding gene editing and the advantages of this action. The aim of this paper is to analyze the newest approaches in genetics and molecular sciences regarding four of the most important neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. We intend through this review to focus on the newest treatment, diagnosis, and predictions regarding this large group of diseases, in order to obtain a more accurate analysis and to identify the emerging signs that could lead to a better outcome in order to increase both the quality and the life span of the patient. Moreover, this review could provide evidence of future possible novel therapies that target the specific genes and that could be useful to be taken into consideration when the classical approaches fail to shed light.


Assuntos
Doença de Alzheimer , Esclerose Lateral Amiotrófica , Doença de Huntington , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doenças Neurodegenerativas/genética , Doença de Huntington/genética , Doença de Alzheimer/genética , Doença de Parkinson/genética , Esclerose Lateral Amiotrófica/genética
6.
Int J Mol Sci ; 24(16)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37629187

RESUMO

Neurodegenerative disorders often acquire due to genetic predispositions and genomic alterations after exposure to multiple risk factors. The most commonly found pathologies are variations of dementia, such as frontotemporal dementia and Lewy body dementia, as well as rare subtypes of cerebral and cerebellar atrophy-based syndromes. In an emerging era of biomedical advances, molecular-cellular studies offer an essential avenue for a thorough recognition of the underlying mechanisms and their possible implications in the patient's symptomatology. This comprehensive review is focused on deciphering molecular mechanisms and the implications regarding those pathologies' clinical advancement and provides an analytical overview of genetic mutations in the case of neurodegenerative disorders. With the help of well-developed modern genetic investigations, these clinically complex disturbances are highly understood nowadays, being an important step in establishing molecularly targeted therapies and implementing those approaches in the physician's practice.


Assuntos
Demência Frontotemporal , Doença por Corpos de Lewy , Humanos , Atrofia , Demência Frontotemporal/genética , Demência Frontotemporal/terapia , Predisposição Genética para Doença , Genômica
7.
Int J Mol Sci ; 24(22)2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-38003309

RESUMO

With the inexorable aging of the global populace, neurodegenerative diseases (NDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) pose escalating challenges, which are underscored by their socioeconomic repercussions. A pivotal aspect in addressing these challenges lies in the elucidation and application of biomarkers for timely diagnosis, vigilant monitoring, and effective treatment modalities. This review delineates the quintessence of biomarkers in the realm of NDs, elucidating various classifications and their indispensable roles. Particularly, the quest for novel biomarkers in AD, transcending traditional markers in PD, and the frontier of biomarker research in ALS are scrutinized. Emergent susceptibility and trait markers herald a new era of personalized medicine, promising enhanced treatment initiation especially in cases of SOD1-ALS. The discourse extends to diagnostic and state markers, revolutionizing early detection and monitoring, alongside progression markers that unveil the trajectory of NDs, propelling forward the potential for tailored interventions. The synergy between burgeoning technologies and innovative techniques like -omics, histologic assessments, and imaging is spotlighted, underscoring their pivotal roles in biomarker discovery. Reflecting on the progress hitherto, the review underscores the exigent need for multidisciplinary collaborations to surmount the challenges ahead, accelerate biomarker discovery, and herald a new epoch of understanding and managing NDs. Through a panoramic lens, this article endeavors to provide a comprehensive insight into the burgeoning field of biomarkers in NDs, spotlighting the promise they hold in transforming the diagnostic landscape, enhancing disease management, and illuminating the pathway toward efficacious therapeutic interventions.


Assuntos
Doença de Alzheimer , Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/metabolismo , Doença de Parkinson/diagnóstico , Doença de Parkinson/metabolismo , Doença de Alzheimer/diagnóstico , Biomarcadores/metabolismo
8.
Mol Reprod Dev ; 88(1): 67-79, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33244844

RESUMO

This study deals with the effect of plasminogen/plasmin on the in vitro maturation (IVM) of bovine cumulus-oocyte complexes (COCs). Exogenous plasminogen activator streptokinase (SK) added to the IVM medium revealed similar values of cumulus expansion and oocyte nuclear maturation compared to controls (standard IVM medium). However, a decrease in both determinations was observed in COCs matured with the supplementation of ɛ-aminocaproic acid (ɛ-ACA), a specific plasmin inhibitor. After in vitro fertilization, no differences were observed in either cleavage or blastocyst rates between SK and control groups; however, ε-ACA treatment caused a decrease in both developmental rates. Zona pellucida (ZP) digestion time decreased in the SK group while it increased in the ε-ACA group. Raman microspectroscopy revealed an increase in the intensity of the band corresponding to the glycerol group of sialic acid in the ZP of oocytes matured with SK, whereas ZP spectra of oocytes treated with ɛ-ACA presented similarities with immature oocytes. The results indicate that although treatment with SK did not alter oocyte developmental competence, it induced modifications in the ZP of oocytes that could modify the folding of glycoproteins. Plasmin inhibition impairs oocyte maturation and has an impact on embryo development, thus evidencing the importance of this protease during IVM.


Assuntos
Células do Cúmulo/metabolismo , Fibrinolisina/farmacologia , Fibrinolíticos/farmacologia , Técnicas de Maturação in Vitro de Oócitos/métodos , Oócitos/metabolismo , Oogênese/efeitos dos fármacos , Plasminogênio/farmacologia , Ácido Aminocaproico/farmacologia , Animais , Blastocisto/efeitos dos fármacos , Blastocisto/metabolismo , Bovinos , Meios de Cultura , Células do Cúmulo/efeitos dos fármacos , Técnicas de Cultura Embrionária/métodos , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Fertilização in vitro/métodos , Fibrinolisina/antagonistas & inibidores , Oócitos/efeitos dos fármacos , Zona Pelúcida/efeitos dos fármacos , Zona Pelúcida/metabolismo
9.
Biochim Biophys Acta Mol Cell Res ; 1864(9): 1459-1468, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28390906

RESUMO

Storage of non-polar lipids in ubiquitous eukaryotic organelles, lipid droplets (LDs), prevents the toxic consequences of unesterified fatty acids and provides a lipid reservoir that can be promptly used to satisfy cellular needs under multiple metabolic and physiological conditions. Tight temporal and spatial control of LD biogenesis and mobilization of neutral lipids is essential for the correct channelling of lipid intermediates to their various cellular destinations and the maintenance of cellular homeostasis. These functions are mediated by multiple interactions between LDs and other intracellular organelles that are required for the delivery of stored lipids. Here we review recent advances in the interactions of LDs with the endoplasmic reticulum (ER), mitochondria and vacuole/lysosome. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann.


Assuntos
Homeostase , Membranas Intracelulares/metabolismo , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos , Animais , Humanos , Proteínas Associadas a Gotículas Lipídicas/genética , Proteínas Associadas a Gotículas Lipídicas/metabolismo
10.
Inorg Chem ; 54(21): 10250-5, 2015 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-26479903

RESUMO

The crystal structure and the Yb valence of the YbFe2Ge2 heavy fermion compound was measured at room temperature and under high pressures using high-pressure powder X-ray diffraction and X-ray absorption spectroscopy via both partial fluorescence yield and resonant inelastic X-ray emission techniques. The measurements are complemented by first-principles density functional theoretical calculations using the self-interaction corrected local spin density approximation investigating in particular the magnetic structure and the Yb valence. While the ThCr2Si2-type tetragonal (I4/mmm) structure is stable up to 53 GPa, the X-ray emission results show an increase of the Yb valence from v = 2.72(2) at ambient pressure to v = 2.93(3) at ∼9 GPa, where at low temperature a pressure-induced quantum critical state was reported.

11.
J Biol Chem ; 288(40): 29124-33, 2013 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-23970552

RESUMO

In the yeast Saccharomyces cerevisiae, the DGK1-encoded diacylglycerol kinase catalyzes the CTP-dependent phosphorylation of diacylglycerol to form phosphatidate. This enzyme, in conjunction with PAH1-encoded phosphatidate phosphatase, controls the levels of phosphatidate and diacylglycerol for phospholipid synthesis, membrane growth, and lipid droplet formation. In this work, we showed that a functional level of diacylglycerol kinase is regulated by the Reb1p transcription factor. In the electrophoretic mobility shift assay, purified recombinant Reb1p was shown to specifically bind its consensus recognition sequence (CGGGTAA, -166 to -160) in the DGK1 promoter. Analysis of cells expressing the PDGK1-lacZ reporter gene showed that mutations (GT→TG) in the Reb1p-binding sequence caused an 8.6-fold reduction in ß-galactosidase activity. The expression of DGK1(reb1), a DGK1 allele containing the Reb1p-binding site mutation, was greatly lower than that of the wild type allele, as indicated by analyses of DGK1 mRNA, Dgk1p, and diacylglycerol kinase activity. In the presence of cerulenin, an inhibitor of de novo fatty acid synthesis, the dgk1Δ mutant expressing DGK1(reb1) exhibited a significant defect in growth as well as in the synthesis of phospholipids from triacylglycerol mobilization. Unlike DGK1, the DGK1(reb1) expressed in the dgk1Δ pah1Δ mutant did not result in the nuclear/endoplasmic reticulum membrane expansion, which occurs in cells lacking phosphatidate phosphatase activity. Taken together, these results indicate that the Reb1p-mediated regulation of diacylglycerol kinase plays a major role in its in vivo functions in lipid metabolism.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Metabolismo dos Lipídeos , Proteínas Repressoras/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Fatores de Transcrição/metabolismo , Sequência de Bases , Sítios de Ligação , Núcleo Celular/metabolismo , Retículo Endoplasmático/metabolismo , Ácidos Graxos/biossíntese , Regulação Enzimológica da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Genes Reporter , Metabolismo dos Lipídeos/genética , Dados de Sequência Molecular , Mutação/genética , Fosfolipídeos/biossíntese , Regiões Promotoras Genéticas/genética , Ligação Proteica/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/genética , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/genética , Triglicerídeos/metabolismo , beta-Galactosidase/metabolismo
12.
Reprod Biol ; 24(1): 100844, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38160587

RESUMO

Components of the plasminogen/plasmin system, known to be present in the oocyte, play a key role in maturation and fertilization. The objective of this study was to examine the effect of plasminogen activation and plasmin inhibition by exogenous supplementation of the IVF medium with streptokinase (SK) or ɛ-aminocaproic acid (ε-ACA), respectively, on fertilization parameters and preimplantation embryo development. After in vitro maturation, bovine cumulus-oocyte complexes (COCs) were inseminated in the presence of SK or ε-ACA. The addition of SK to the IVF medium facilitated the adhesion of the spermatozoa to the zona pellucida without affecting the percentages of monospermy. Cleavage rates and blastocyst yield were similar between the SK and Control groups while they were lower with the ε-ACA treatment. Additionally, we found that the expression levels of embryo quality-related genes (SDHA and DNMT3A) could be modified in blastocysts by the addition of SK or ε-ACA during IVF. The results obtained indicate that supplementation of the IVF medium with SK did not greatly alter the embryonic developmental parameters related to embryo quality in blastocysts. Moreover, we noticed that ε-ACA treatment compromises the success of in vitro embryo development, thus highlighting the importance of the plasminogen/plasmin activity during the early stages of embryogenesis in bovine.


Assuntos
Desenvolvimento Embrionário , Fibrinolisina , Animais , Bovinos , Feminino , Masculino , Gravidez , Blastocisto/metabolismo , Desenvolvimento Embrionário/fisiologia , Fertilização , Fertilização in vitro/veterinária , Fertilização in vitro/métodos , Fibrinolisina/metabolismo , Oócitos , Plasminogênio/metabolismo
13.
Cureus ; 16(3): e56982, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38665758

RESUMO

The Golgi apparatus is an organelle responsible for protein processing, sorting, and transport in cells. Recent research has shed light on its possible role in the pathogenesis of various bone diseases. This review seeks to explore its significance in osteoporosis, osteogenesis imperfecta, and other bone conditions such as dysplasias. Numerous lines of evidence demonstrate that perturbations to Golgi apparatus function can disrupt post-translational protein modification, folding and trafficking functions crucial for bone formation, mineralization, and remodeling. Abnormalities related to glycosylation, protein sorting, or vesicular transport in Golgi have been associated with altered osteoblast and osteoclast function, compromised extracellular matrix composition, as well as disrupted signaling pathways involved with homeostasis of bones. Mutations or dysregulation of Golgi-associated proteins, including golgins and coat protein complex I and coat protein complex II coat components, have also been implicated in bone diseases. Such genetic alterations may disrupt Golgi structure, membrane dynamics, and protein transport, leading to bone phenotype abnormalities. Understanding the links between Golgi apparatus dysfunction and bone diseases could provide novel insights into disease pathogenesis and potential therapeutic targets. Future research should focus on unraveling specific molecular mechanisms underlying Golgi dysfunction associated with bone diseases to develop targeted interventions for restoring normal bone homeostasis while decreasing clinical manifestations associated with these issues.

14.
Cureus ; 16(1): e51596, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38313911

RESUMO

This case report elucidates the clinical and surgical journey of a 62-year-old patient with a history of multiple comorbidities including a severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infection, presenting with temporospatial disorientation, bradypsychia, and bradyphasia, without motor deficits, diagnosed with sarcomatous meningioma and skull lysis. Amidst the complexities of managing primary brain tumors, this report underscores the significance of thorough morphopathological examination, while considering patient demographics and tumor localization in assessing the nature of the neoplasm. It highlights meningiomas as predominantly benign yet stemming from monoclonal proliferation, with their occurrence influenced by genetic predispositions and environmental factors such as ionizing radiation exposure. The intricate case details multiple surgical interventions necessitated by complications such as wound dehiscence and cerebrospinal fluid leaks, managed successfully through a tailored neurosurgical approach and meticulous postoperative care. This narrative reinforces the pivotal role of interdisciplinary collaboration, with substantial contributions from radiology, anesthesiology, intensive care, cardiology, infectious disease, and rehabilitation medicine in achieving favorable outcomes. The discussion contextualizes the patient's condition within the broader neurosurgical literature, reflecting on the prognostic factors associated with giant meningiomas and the impact of factors like age and tumor location on resection outcomes. The case also delves into the efficacy of Gamma Knife radiosurgery in long-term tumor control, drawing on retrospective analyses. In conclusion, the case report advocates for a nuanced, individualized treatment, where the integration of multiple disciplines and responsive management of postoperative complications is critical to patient recovery. The successful resolution of this patient's condition exemplifies the quintessential nature of interdisciplinary collaboration and highlights the potential for optimizing neurosurgical protocols in the context of complex patient profiles.

15.
Cureus ; 16(5): e60824, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38910700

RESUMO

Intracranial "kissing" aneurysms are rare vascular conditions described as two anatomically adjacent aneurysms originating from either the same or different arteries, with their walls pressed together. Two-dimensional angiography was formerly considered the gold standard for diagnosis, with the three-dimensional rotational type now offering more insightful details about vascular discrepancies. The treatment of anterior communicating artery (AcoA) "kissing" aneurysms poses significant challenges, with surgical clipping proving difficult due to their deep midline location or the bilateral anterograde arterial supply. However, advancements in endovascular coil embolization, such as dual-volume reconstruction, can assist in diagnosis. This study presents the case of a 50-year-old patient who was diagnosed with "kissing" aneurysms of the AcoA. The patient underwent surgical clipping and showed no pathological follow-up findings. The surgical intervention often provides a more direct and effective approach. This case contributes to the body of knowledge surrounding the management of this complex disease.

16.
Cells ; 13(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891028

RESUMO

Cervical cancer (CC) remains among the most frequent cancers worldwide despite advances in screening and the development of vaccines against human papillomavirus (HPV), involved in virtually all cases of CC. In mid-income countries, a substantial proportion of the cases are diagnosed in advanced stages, and around 40% of them are diagnosed in women under 49 years, just below the global median age. This suggests that members of this age group share common risk factors, such as chronic inflammation. In this work, we studied samples from 46 patients below 45 years old, searching for a miRNA profile regulating cancer pathways. We found 615 differentially expressed miRNAs between tumor samples and healthy tissues. Through bioinformatic analysis, we found that several of them targeted elements of the JAK/STAT pathway and other inflammation-related pathways. We validated the interactions of miR-30a and miR-34c with JAK1 and STAT3, respectively, through dual-luciferase and expression assays in cervical carcinoma-derived cell lines. Finally, through knockdown experiments, we observed that these miRNAs decreased viability and promoted proliferation in HeLa cells. This work contributes to understanding the mechanisms through which HPV regulates inflammation, in addition to its canonical oncogenic function, and brings attention to the JAK/STAT signaling pathway as a possible diagnostic marker for CC patients younger than 45 years. To our knowledge to date, there has been no previous description of a panel of miRNAs or even ncRNAs in young women with locally advanced cervical cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica , Inflamação , MicroRNAs , Fator de Transcrição STAT3 , Transdução de Sinais , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais/genética , Adulto , Inflamação/genética , Inflamação/patologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Células HeLa , Janus Quinase 1/metabolismo , Janus Quinase 1/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Pessoa de Meia-Idade
17.
Cureus ; 16(6): e62462, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38882229

RESUMO

This retrospective mono-center study focuses on 144 cases of glioblastoma treated over a time span of 12 years in our clinic in Romania. We offer critical insight into the dreadful aspect of this tumor by highlighting the principal characteristics such as localization, the genetic information of each case, progression-free survival (PFS), and overall survival (OS). A tenth of our patients underwent a second surgical procedure, providing a comparable OS to the other part of our study group, proving that surgical treatment as salvage therapy is a viable option. Also, our research reinforces the fact that utilizing the Karnofsky Performance Scale is a great predictor of patient outcomes in glioblastoma patients. Even though radiotherapy and chemotherapy have mild effects in the context of this oncological disease, our research shows that O6-methylguanine-DNA methyltransferase (MGMT) methylation status and epidermal growth factor receptor (EGFR) amplification have an important effect on OS. Moreover, the particularity of our study, that our patients did not start adjuvant therapy right after surgery, highlighted by a low OS compared to the international literature, sheds light on the fact that chemotherapy and radiotherapy must be started right after the surgical procedure, according to the Stupp protocol. To sum up, our research takes into consideration the factors that influence patient survival and outcome in the battle against glioblastoma.

18.
Cureus ; 16(3): e56933, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38665760

RESUMO

This comprehensive study analyzes 346 surgically treated intracranial aneurysms, emphasizing the importance of understanding risk factors and prevalent characteristics in patients. Intracranial aneurysms, primarily of the saccular or berry type, significantly contribute to nontraumatic subarachnoid hemorrhages and demonstrate a rising incidence due to advances in imaging techniques. The study highlights a gender discrepancy in aneurysm occurrence and a higher prevalence in individuals over 30 years old. The research delves into various aspects, including aneurysm localization, diameter, neck dimensions, and rupture status, with a focus on the anterior communicating artery and middle communicating artery as predominant locations. Significant findings include the prevalence of ruptured aneurysms and the impact of arterial hypertension, atherosclerosis, obesity, and diabetes on aneurysm epidemiology. The study also investigates the occurrence of vasospasm, a significant factor in delayed morbidity and mortality in aneurysmal subarachnoid hemorrhage. The utilization of the Glasgow Outcome Scale and other quantification scales aids in understanding the severity and postoperative outcomes of intracranial aneurysms. Challenges such as the incidence of reopenings and postoperative osteomyelitis are addressed, underlining the need for refined protocols and multidisciplinary approaches in treatment. The study's results contribute to the existing knowledge base on intracranial aneurysms, emphasizing the importance of ongoing research and tailored treatment strategies. The comprehensive nature of this analysis, covering preoperative, intraoperative, and postoperative factors, provides valuable insights into the complex interplay of risk factors and clinical outcomes in patients with intracranial aneurysms.

19.
Environ Monit Assess ; 185(7): 5883-90, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23138419

RESUMO

The gas station attendants are exposed daily to chemical agents that compose gasoline, such as BTEX (benzene, toluene, ethylbenzene, and xylene), and the exposure to these agents can cause a variety of effects on the human health. Among the various possible cell alterations associated with these exposures are the formation of micronuclei and of binucleated cells which are used as indicators of clastogenic action. Benzene, the main carcinogenic agent, is metabolized to more soluble forms and easily excreted by isoenzymes of cytochrome P450, such as CYP1A1. The CYP1A1 gene is highly polymorphic and one of its allele variations can be detected by the use of restriction endonucleasis MspI and is originated by the transition of a thymine by a cytosine (3798T>C), resulting in the polymorphic allele CYP1A1*2A. The objective of this study was to evaluate the cytogenetic damage induced by the exposure to BTEX and to associate it with the polymorphisms of the CYP1A1 and NR1I3 genes. Samples of exfoliated cells from the oral mucosa of 27 gas station attendants and from a control group were collected. The results found show that the group exposed to BTEX presents significantly higher alterations than those in the control group for micronuclei (MN; 6.85 ± 1.33 vs. 2.96 ± 1.91, P < 0.001) and for the total of nuclear alterations observed (MN + binucleated cells (BNC); 9.59 ± 4.73 vs. 5.07 ± 2.21, P < 0.001). When comparing the cytological alterations and the genotypes among the exposed individuals for the polymorphism 3798T>C of the CYP1A1 gene, homozygotes TT present MN + BNC significantly higher than carriers of the allele C (10.88 ± 5.36 vs. 5.33 ± 2.52, P = 0.028). No association was observed in the control group or for the NR1I3 gene. These results show that molecular and cytogenetic data can be used in the future as tools to monitor individuals exposed to such compounds.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Derivados de Benzeno/toxicidade , Citocromo P-450 CYP1A1/genética , Mutagênicos/toxicidade , Exposição Ocupacional/análise , Receptores Citoplasmáticos e Nucleares/genética , Adulto , Benzeno/toxicidade , Receptor Constitutivo de Androstano , Citocromo P-450 CYP1A1/metabolismo , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Receptores Citoplasmáticos e Nucleares/metabolismo , Tolueno/toxicidade , Xilenos/toxicidade , Adulto Jovem
20.
Rev Int Androl ; 21(4): 100368, 2023.
Artigo em Espanhol | MEDLINE | ID: mdl-37399729

RESUMO

The sexual manifestations of residents in long-term care facilities are often overlooked and even discouraged by care staff. The aim of this study was to conduct a systematic review of caregivers' attitudes, knowledge and perceptions of sexual expression. After consulting different databases, ten scientific articles published between 2012 and 2022 met the inclusion criteria to form part of this review. This work has made it possible to identify and structure the insufficient scientific literature on this specific area of sexuality in older adults. It is concluded that there is scarce scientific literature and that the areas reviewed are determinant in the daily care of institutionalised older adults. Expanding in this field of study will allow the creation of training programmes and the creation of programmes for the care staff to deal with the sexual behaviour of institutionalised older adults.


Assuntos
Assistência de Longa Duração , Casas de Saúde , Humanos , Idoso , Comportamento Sexual , Sexualidade , Atitude
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