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The outbreak of the coronavirus disease 2019 (COVID-19) has gathered 1 year of scientific/clinical information. This informational asset should be thoroughly and wisely used in the coming year colliding in a global task force to control this infection. Epidemiology of this infection shows that the available estimates of SARS-CoV-2 infection prevalence largely depended on the availability of molecular testing and the extent of tested population. Within molecular diagnosis, the viability and infectiousness of the virus in the tested samples should be further investigated. Moreover, SARS-CoV-2 has a genetic normal evolution that is a dynamic process. The immune system participates to the counterattack of the viral infection by pathogen elimination, cellular homoeostasis, tissue repair and generation of memory cells that would be reactivated upon a second encounter with the same virus. In all these stages, we still have knowledge to be gathered regarding antibody persistence, protective effects and immunological memory. Moreover, information regarding the intense pro-inflammatory action in severe cases still lacks and this is important in stratifying patients for difficult to treat cases. Without being exhaustive, the review will cover these important issues to be acknowledged to further advance in the battle against the current pandemia.
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Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Teste para COVID-19 , COVID-19 , SARS-CoV-2 , Animais , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/imunologia , Humanos , Memória Imunológica , Mutação , Pandemias , SARS-CoV-2/genética , SARS-CoV-2/imunologiaRESUMO
Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been recently applied in detection of carbapenemase-producing Gram-negative isolates. In the present study, we review the latest developments in this field.
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Proteínas de Bactérias/análise , Bactérias Gram-Negativas/enzimologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , beta-Lactamases/análise , HumanosRESUMO
Merkel cell polyomavirus (MCPyV) is a newly discovered human small, non-enveloped, double-stranded DNA virus, which was classified into the Polyomaviridae family. MCPyV is acquired in early childhood through close contact involving respiratory tract secretions and causes a widespread, previously unrecognised, asymptomatic infection in both immunocompetent children and adults. To date, several researchers have established that MCPyV is the potential causative agent of Merkel cell carcinoma, a relatively rare but life-threatening skin cancer of neuroendocrine origin. In our review, we present current data on the presence of MCPyV DNA in children and address the possible role that the respiratory tract plays in the route of viral transmission. Future studies are required to fully elucidate the potential implications of MCPyV infection in children.
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Carcinoma de Célula de Merkel/virologia , Poliomavírus das Células de Merkel/fisiologia , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/virologia , Adolescente , Adulto , Carcinoma de Célula de Merkel/epidemiologia , Criança , Pré-Escolar , Humanos , Poliomavírus das Células de Merkel/genética , Infecções por Polyomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Adulto JovemRESUMO
Twenty five years have passed since the first research efforts in Greece on human papillomavirus (HPV) performed by the Department of Clinical Virology at the University of Crete School of Medicine. HPV infection in the human cervix was initially evaluated in relation to the host mutational and transcriptional activation of the ras/raf genes pathway, p53 gene polymorphisms, neo-angiogenesis- related gene expression and G1/S phase transition. A series of epidemiological studies ensued, evaluating HPV infection in the ophthalmic pterygium, benign laryngeal tumors, parotid lesions, nasal polyposis, actinic keratosis, aborted material and non-genital cancers. The observed geographical variations of different HPV types within the Hellenic population indicated a higher prevalence of HPV 18 on the island of Crete compared to mainland Greece. Moreover, our research led to the investigation of the mother-to-infant HPV transmission via human breast milk and the detection of novel HPV types in juvenile recurrent respiratory papillomatosis. We also evaluated the presence of HPV in the respiratory tract of asymptomatic children and the relationship between maternal HPV infection and neonatal prematurity. Despite the introduction of the current prophylactic vaccines against HPV into clinical practice, HPV remains a challenging target for the next generation of researchers, as the war against HPV continues.
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Pesquisa Biomédica/história , Papillomaviridae , Infecções por Papillomavirus/história , Faculdades de Medicina/história , Universidades/história , Virologia/história , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Grécia/epidemiologia , História do Século XX , História do Século XXI , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/história , Masculino , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/transmissão , Vacinas contra Papillomavirus/história , Gravidez , Prevalência , Infecções Respiratórias/históriaRESUMO
Human papillomaviruses (HPVs) infection and HPVs-associated lesions, including skin warts in children and adults and cervical neoplasia in women, have been excessively studied since ancient years. In our article, we present briefly four major researchers from the HPVs pre-vaccination historic period: Hippokrates the Asclepiad, Domenico Antonio Rigoni-Stern, George N. Papanicolaou and Harald zur Hausen.
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Infecções por Papillomavirus/história , Pesquisa Biomédica/história , Feminino , História do Século XIX , História do Século XX , Humanos , Vacinas contra Papillomavirus/imunologiaRESUMO
Human papillomavirus (HPV) is the etiologic risk factor for cervical cancer. Some studies have suggested an association with a subset of lung tumors, but the etiologic link has not been firmly established. We performed an international pooled analysis of cross-sectional studies (27 datasets, n = 3249 patients) to evaluate HPV DNA prevalence in lung cancer and to investigate viral presence according to clinical and demographic characteristics. HPV16/18 were the most commonly detected, but with substantial variation in viral prevalence between geographic regions. The highest prevalence of HPV16/18 was observed in South and Central America, followed by Asia, North America and Europe (adjusted prevalence rates = 22, 5, 4 and 3%, respectively). Higher HPV16 prevalence was noted in each geographic region compared with HPV18, except in North America. HPV16/18-positive lung cancer was less likely observed among White race (adjusted odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.12-0.90), whereas no associations were observed with gender, smoking history, age, histology or stage. Comparisons between tumor and normal lung tissue show that HPV was more likely to be present in lung cancer rather than normal lung tissues (OR = 3.86, 95% CI = 2.87-5.19). Among a subset of patients with HPV16-positive tumors, integration was primarily among female patients (93%, 13/14), while the physical status in male cases (N = 14) was inconsistent. Our findings confirm that HPV DNA is present in a small fraction of lung tumors, with large geographic variations. Further comprehensive analysis is needed to assess whether this association reflects a causal relationship.
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Alphapapillomavirus/genética , Neoplasias Pulmonares/etiologia , Infecções por Papillomavirus/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Prevalência , Integração ViralRESUMO
BACKGROUND: The human KCNE1 protein forms the ß-subunit of the IKs potassium channel and is important in the regulation of the atrial action potential duration. The purpose of this study was to investigate the association between the nonsynonymous 112G>A mutation of the KCNE1 gene and postcardiac surgery atrial fibrillation (AF). METHODS AND RESULTS: A cohort of patients scheduled for cardiac surgery was prospectively recruited. The genotype of 112G>A polymorphism was determined using polymerase chain reaction/restriction fragment analysis and confirmed with direct sequencing of the polymerase chain reaction product. In total, 509 patients were recruited in the study, of whom 203 (39.9%) had at least 1 qualifying episode of postoperative AF. An increased frequency of the G allele was observed in the postoperative AF group compared with the group without postoperative AF (0.628 vs 0.552, respectively, P = .016). The individual's relative risk of postoperative AF increased as the number of G alleles increased from 1.36 (95% CI 0.89-2.08) for G allele heterozygotes to 1.62 (95% CI 1.08-2.43) for G allele homozygotes (P = .04 for trend). The multivariate analysis revealed the abnormal ejection fraction (odds ratio [OR] 1.585, 95% CI 1.076-2.331, P = .020), age (OR 1.043, 95% CI 1.022-1.064, P < .001), type of surgery (aortic valve replacement) (OR 1.869, 95% CI 1.094-3.194, P = .022), and the 112G>A genotype (OR 1.401 [in additive model], 95% CI 1.052-1.865, P = .021) to be independent predictors of postoperative AF. CONCLUSION: This study confirmed the association of the 112G>A polymorphism and postoperative AF in a cohort of patients undergoing cardiac surgery.
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Fibrilação Atrial/genética , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , DNA/genética , Isquemia Miocárdica/cirurgia , Polimorfismo Genético , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Idoso , Alelos , Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Feminino , Seguimentos , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Período Pós-Operatório , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Estudos Prospectivos , Fatores de RiscoRESUMO
p53 is a tumour suppressor gene with an established role in the majority of human neoplasias. Its homologues-p63 and p73-cannot be classified as tumour suppressors, since they encode isoforms with oncogenic properties as well. p63 plays a crucial role in epithelial cell differentiation and p73 is essential for neuronal cell development. The p63 and p73 expressions have been investigated in a variety of human tumours including bladder carcinomas; yet, this is the first study to simultaneously analyse the transcriptional levels of all p53 family members in bladder cancer. Using quantitative real-time polymerase chain reaction, we measured the mRNA expression of p53, p63 and p73 in 30 bladder tumours, each paired with adjacent normal tissue. All three studied genes were up-regulated in malignant specimens, p53 by 1.9-fold, p63 by threefold and p73 by twofold, respectively. Further analysis suggested that p63 and p73 act independently of p53 in the malignant bladder epithelium. Statistical analysis revealed that p63 overexpression was more frequent in recurrent bladder tumours (p = 0.045) and in older patients (p = 0.022). Papillary tumours also exhibited abnormal p63 expression (p = 0.026). Finally, p73 was up-regulated in Grade III one-site tumours (p = 0.040). Our results indicate that all p53 family members are abnormally expressed in bladder cancer but do not act synergistically. High levels of p63 correlate with non-muscle invasive tumours with frequent relapses, whereas p73 overexpression is associated with a more aggressive tumour phenotype.
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Proteínas de Ligação a DNA/biossíntese , Proteínas de Membrana/biossíntese , Recidiva Local de Neoplasia/genética , Proteínas Nucleares/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Proteínas Supressoras de Tumor/biossíntese , Neoplasias da Bexiga Urinária/genética , Idoso , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Masculino , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Proteínas Nucleares/análise , Proteínas Nucleares/genética , Isoformas de Proteínas/genética , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Proteína Tumoral p73 , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/análise , Proteínas Supressoras de Tumor/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologiaRESUMO
The presence of a dysregulated NF-κB/Snail/YY1/RKIP loop was recently established in metastatic prostate cancer cells and non-Hodgkin's lymphoma; however, its involvement in multiple myeloma (MM) has yet to be investigated. Aim of the study was to investigate the role of the NF-κB/Snail/YY1/RKIP circuitry in MM and how each gene is correlated with the remaining genes of the loop. Using gene set enrichment analysis and gene neighbours analysis in data received from four datasets included in the Multiple Myeloma Genomics Portal of the Multiple Myeloma Research Consortium, we identified various enriched gene sets associated with each member of the NF-κB/Snail/YY1/RKIP circuitry. In each dataset, the 20 most co-expressed genes with the circuitry genes were isolated subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Among many, we highlighted on FNDC3B, TPD52, BBX, MBNL1 and MFAP2. Many co-expressed genes participated in the regulation of metabolic processes and nucleic acid binding, or were transcription factor binding genes and genes with metallopeptidase activity. The transcription factors FOXO4, GATA binding factor, Sp1 and AP4 most likely affect the expression of the NF-κB/Snail/YY1/RKIP circuitry genes. Computational analysis of various GEO datasets revealed elevated YY1 and RKIP levels in MM vs. the normal plasma cells, as well as elevated RKIP levels in MM vs. normal B lymphocytes. The present study highlights the relationships of the NF-κB/Snail/YY1/RKIP circuitry genes with specific cancer-related gene sets in multiple myeloma.
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Mieloma Múltiplo/genética , NF-kappa B/genética , Proteína de Ligação a Fosfatidiletanolamina/genética , Fatores de Transcrição/genética , Fator de Transcrição YY1/genética , Proteínas de Ciclo Celular , Fibronectinas/genética , Humanos , Proteínas Nucleares/genética , Fatores de Transcrição da Família SnailRESUMO
The cytochrome P450 CYP1A1 and CYP1B1 enzymes are phase I extrahepatic enzymes involved in the activation of pro-carcinogenic compounds to carcinogenic metabolites. Although differential overexpression of CYP1A1 and CYP1B1 has been documented at the messenger RNA (mRNA) and protein level, studies that have examined CYP1 expression by enzyme activity assays are limited. In the current study, the expression of CYP1A1 and CYP1B1 was investigated in a panel of human tumors of endometrial origin by quantitative reverse transcriptase PCR (qRT-PCR), Western blotting, and enzyme activity assays. The data revealed that approximately 36 % (5/14) and 43 % (6/14) of the endometrial tumors overexpressed CYP1A1 and CYP1B1 mRNA, whereas in 57 % of the endometrial tumors, CYP1 mRNA levels were downregulated. The mean mRNA levels of CYP1B1 and CYP1A1 in endometrial tumors did not show a significant difference compared to normal tissues (p > 0.05). Western blotting confirmed the qRT-PCR results and CYP1A1 and CYP1B1 proteins were shown to be downregulated in 7/14 (50 %) of the tumors and overexpressed in 4/14 (29 %) of the tumors. As regards to enzyme activity, 21 % (3/14) of the endometrial samples revealed elevated CYP1 activity levels across the tumor counterparts. Overall, the data suggest a putative downregulation of CYP1A1 and CYP1B1 expression in endometrial tumors, whereas overexpression of active CYP1 enzymes in 21 % of the tumors highlights the potential use of the latter enzymes as chemotherapeutic targets in endometrial cancer.
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Biomarcadores Tumorais/análise , Citocromo P-450 CYP1A1/biossíntese , Citocromo P-450 CYP1B1/biossíntese , Neoplasias do Endométrio/enzimologia , Idoso , Western Blotting , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP1A1/análise , Citocromo P-450 CYP1B1/análise , Neoplasias do Endométrio/patologia , Feminino , Humanos , Espectrometria de Massas , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TranscriptomaRESUMO
Prostate cancer is the most common neoplasm found in males and the second most frequent cause of cancer-related mortality in males in Greece. Among other pathogens, the detection frequency of human papillomavirus (HPV) has been found to be significantly increased in tumor tissues among patients with sexually transmitted diseases (STDs), depending on the geographical distribution of each population studied. The present study focused on the detection of HPV and the distribution of Arg72Pro p53 polymorphism in a cohort of healthy individuals, as well as prostate cancer patients. We investigated the presence of HPV in 50 paraffin-embedded prostate cancer tissues, as well as in 30 physiological tissue samples from healthy individuals by real-time PCR. Furthermore, the same group of patients was also screened for the presence of the Arg72Pro polymorphism of the p53 gene, a p53 polymorphism related to HPV. Out of the 30 control samples, only 1 was found positive for HPV (3.33 %). On the contrary, HPV DNA was detected in 8 out of the total 50 samples (16 %) in the prostate cancer samples. The distribution of the three genotypes, Arg/Arg, Arg/Pro, and Pro/Pro, was 69.6, 21.7, and 8.7 % in the cancer patients and 75.0, 17.86, and 7.14 % in healthy controls, respectively. No statistically significant association was observed between the HPV presence and the age, stage, p53 polymorphism status at codon 72, or PSA. The increased prevalence of HPV detected in the prostate cancer tissues is in agreement with that reported in previous studies, further supporting the association of HPV infection and prostate cancer.
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Alphapapillomavirus/genética , Códon , Infecções por Papillomavirus/complicações , Polimorfismo Genético , Neoplasias da Próstata/genética , Neoplasias da Próstata/virologia , Proteína Supressora de Tumor p53/genética , Idoso , Substituição de Aminoácidos , Estudos de Casos e Controles , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/patologiaRESUMO
Although the role of human papillomavirus (HPV) in the development of uterine cervical cancer is well established, the role of HPV in lung carcinogenesis remains controversial. The detection rates of HPV DNA are subject to a wide variation from 0 to 100%. This is partly influenced by the detection techniques employed. To elucidate the impact of HPV infection on lung parenchyma, we analyzed 100 non-small cell lung cancer (NSCLC) specimens (39 squamous cell carcinomas, 50 adenocarcinomas, 5 samples with characteristics of both squamous cell and adenocarcinoma, 5 undifferentiated and 1 large cell carcinoma) from the region of Crete, Greece. Sixteen non-cancerous samples served as the negative controls. DNA was extracted from 100 paraffin-embedded tissue sections obtained from NSCLC patients. The specimens were examined for the detection of HPV DNA by Real-Time PCR using GP5+/GP6+ primers. Furthermore, the HPV-positive samples were subjected to genotyping. In contrast to the absence of viral genomes in the control samples, HPV DNA was detected in 19 NSCLC specimens (19%). In particular, 4 squamous cell carcinomas, 12 adenocarcinomas, 1 sample with characteristics of both squamous cell and adenocarcinoma, and 2 undifferentiated samples were HPV-positive. The distribution of HPV genotypes was as follows: HPV 16: eight cases (42.1%); HPV 11: three cases (15.8%); HPV 6: one case (5.2%); HPV 59: one case (5.2%); HPV 33: two cases (10.5%); HPV 31: two cases (10.5%) and HPV 18: two cases (10.5%). The presence of HPV in the tumor samples provides evidence of the potential role of HPV in NSCLC and strongly argues for additional research on this issue.
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Carcinoma Pulmonar de Células não Pequenas/virologia , Neoplasias Pulmonares/virologia , Papillomaviridae/isolamento & purificação , Idoso , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , DNA Viral/análise , Feminino , Volume Expiratório Forçado , Genótipo , Humanos , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Capacidade VitalRESUMO
Allicin is a thiosulphate molecule produced in garlic (Allium sativum) and has a wide range of biological actions and pharmaceutical applications. Its precursor molecule is the non-proteinogenic amino acid alliin (S-allylcysteine sulphoxide). The alliin biosynthetic pathway in garlic involves a group of enzymes, members of which are the γ-glutamyl-transpeptidase isoenzymes, Allium sativum γ-glutamyl-transpeptidase AsGGT1, AsGGT2 and AsGGT3, which catalyze the removal of the γ-glutamyl group from γ-glutamyl-S-allyl-L-cysteine to produce S-allyl-L-cysteine. This removal is followed by an S-oxygenation, which leads to the biosynthesis of alliin. The aim of the present study is to annotate previously discovered genes of garlic γ-glutamyl-transpeptidases, as well as a fourth candidate gene (AsGGT4) that has yet not been described. The annotation includes identifying the loci of the genes in the garlic genome, revealing the overall structure and conserved regions of these genes, and elucidating the evolutionary history of these enzymes through their phylogenetic analysis. The genomic structure of γ-glutamyl-transpeptidase genes is conserved; each gene consists of seven exons, and these genes are located on different chromosomes. AsGGT3 and AsGGT4 enzymes contain a signal peptide. To that end, the AsGGT3 protein sequence was corrected; four indel events occurring in AsGGT3 coding regions suggested that at least in the garlic variety Ershuizao, AsGGT3 may be a pseudogene. Finally, the use of protein structure prediction tools allowed the visualization of the tertiary structure of the candidate peptide.
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The present article discusses the interconnectedness of coronavirus disease 2019 (COVID-19) and obesity as global health crises. The similarities between the two conditions are highlighted; these include shared risk factors and comorbidities, and the impact of obesity on the immune system. The present article also mentions the challenges faced in combating both pandemics, including misinformation and prejudice against obesity. It discusses the development of therapeutic medications and vaccines for COVID-19 and the potential of injectable incretin analogues for weight loss. Socioeconomic issues are also addressed, with obesity being more prevalent in lower socioeconomic groups and the cost of obesity treatments being a barrier for those in need. The present article emphasizes the need for comprehensive and sustainable solutions, including public health interventions, education, policy changes and equitable distribution of resources, to address both COVID-19 and obesity.
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Bruxism is a non-functional involuntary muscle activity that affects more than one-third of the population at some point in their lives. A number of factors have been found to be related to the etiopathogenesis of bruxism; therefore, the condition is considered multifactorial. The most commonly accepted factor is stress. Stress has long been considered to increase muscle tone and to reduce the pain threshold. Current evidence indicates that exposure to chronic stress, distress and allostatic load ignite neurological degeneration and the attenuation of critical neuronal pathways that are highly implicated in the orofacial involuntary muscle activity. The present review discusses the negative effects that chronic stress exerts on certain parts of the central nervous system and the mechanisms through which these changes are involved in the etiopathogenesis of bruxism. The extent of these morphological and functional changes on nerves and neuronal tracts provides valuable insight into the obstacles that need to be overcome in order to achieve successful treatment. Additionally, particular emphasis is given on the effects of bruxism on the central nervous system, particularly the activation of the hypothalamic-pituitary-adrenal axis, as this subsequently induces an increase in circulating corticosterone levels, also evidenced by increased levels of salivary cortisol, thereby transforming bruxism into a self-reinforcing loop.
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Coronavirus disease 2019 (COVID19), a systemic illness caused by severe acute respiratory distress syndrome 2 (SARSCoV2), has triggered a worldwide pandemic with symptoms ranging from asymptomatic to chronic, affecting practically every organ. Melatonin, an ancient antioxidant found in all living organisms, has been suggested as a safe and effective therapeutic option for the treatment of SARSCoV2 infection due to its good safety characteristics and broadspectrum antiviral medication properties. Melatonin is essential in various metabolic pathways and governs physiological processes, such as the sleepwake cycle and circadian rhythms. It exhibits oncostatic, antiinflammatory, antioxidant and antiaging properties, exhibiting promise for use in the treatment of numerous disorders, including COVID19. The preventive and therapeutic effects of melatonin have been widely explored in a number of conditions and have been wellestablished in experimental ischemia/reperfusion investigations, particularly in coronary heart disease and stroke. Clinical research evaluating the use of melatonin in COVID19 has shown various improved outcomes, including reduced hospitalization durations; however, the trials are small. Melatonin can alleviate mitochondrial dysfunction in COVID19, improve immune cell function and provide antioxidant properties. However, its therapeutic potential remains underexplored due to funding limitations and thus further investigations are required.
Assuntos
COVID-19 , Melatonina , Humanos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Melatonina/farmacologia , Melatonina/uso terapêutico , Melatonina/metabolismo , Pandemias , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2/metabolismoRESUMO
Head and neck squamous cell carcinomas (HNSCCs), a heterogeneous group of cancers that arise from the mucosal epithelia cells in the head and neck areas, present great challenges in diagnosis, treatment and prognosis due to their complex aetiology and various clinical manifestations. Several factors, including smoking, alcohol consumption, oncogenic genes, growth factors, EpsteinBarr virus and human papillomavirus infections can contribute to HNSCC development. The unpredictable tumour microenvironment adds to the complexity of managing HNSCC. Despite significant advances in therapies, the prediction of outcome after treatment for patients with HNSCC remains poor, and the 5year overall survival rate is low due to late diagnosis. Early detection greatly increases the chances of successful treatment. The present review aimed to bring together the latest findings related to the molecular mechanisms of HNSCC carcinogenesis and progression. Comprehensive genomic, transcriptomic, metabolomic, microbiome and proteomic analyses allow researchers to identify important biological markers such as genetic alterations, gene expression signatures and protein markers that drive HNSCC tumours. These biomarkers associated with the stages of initiation, progression and metastasis of cancer are useful in the management of patients with cancer in order to improve their life expectancy and quality of life.
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Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Microambiente Tumoral , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinogênese/genética , Prognóstico , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/patologiaRESUMO
Due to the addictive qualities of tobacco products and the compulsive craving and dependence associated with their use, nicotine dependence continues to be a serious public health concern on a global scale. Despite awareness of the associated health risks, nicotine addiction contributes to numerous acute and chronic medical conditions, including cardiovascular disease, respiratory disorders and cancer. The nocturnal secretion of pineal melatonin, known as the 'hormone of darkness', influences circadian rhythms and is implicated in addictionrelated behaviors. Melatonin receptors are found throughout the brain, influencing dopaminergic neurotransmission and potentially attenuating nicotineseeking behavior. Additionally, the antioxidant properties of melatonin may mitigate oxidative stress from chronic nicotine exposure, reducing cellular damage and lowering the risk of nicotinerelated health issues. In addition to its effects on circadian rhythmicity, melatonin acting via specific neural receptors influences sleep and mood, and provides neuroprotection. Disruptions in melatonin signaling may contribute to sleep disturbances and mood disorders, highlighting the potential therapeutic role of melatonin in addiction and psychiatric conditions. Melatonin may influence neurotransmitter systems involved in addiction, such as the dopaminergic, glutamatergic, serotonergic and endogenous opioid systems. Preclinical studies suggest the potential of melatonin in modulating reward processing, attenuating druginduced hyperactivity and reducing opioid withdrawal symptoms. Chronotherapeutic approaches targeting circadian rhythms and melatonin signaling show promise in smoking cessation interventions. Melatonin supplementation during periods of heightened nicotine cravings may alleviate withdrawal symptoms and reduce the reinforcing effects of nicotine. Further research is required however, to examine the molecular mechanisms underlying the melatoninnicotine association and the optimization of therapeutic interventions. Challenges include variability in individual responses to melatonin, optimal dosing regimens and identifying biomarkers of treatment response. Understanding these complexities could lead to personalized treatment strategies and improve smoking cessation outcomes.
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Ritmo Circadiano , Melatonina , Tabagismo , Melatonina/metabolismo , Humanos , Tabagismo/metabolismo , Animais , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Nicotina/efeitos adversosRESUMO
Intracranial cavernous malformations (CMs) are vascular lesions with a high bleeding rate. At present, the debate regarding their treatment is still ongoing. The present systematic review and meta-analysis aimed to evaluate the safety of surgery or radiosurgery (SRS) for the management of CMs and to determine their potential outcomes compared with conservative treatment. The present systematic review and meta-analysis investigated the relative articles involving the management of intracranial CMs, namely their natural history (conservative treatment) vs. surgical/SRS treatment through electronic databases until June, 2023. The collected variables included the first author's name, the study period covered, the year of publication, the total number of patients examined and their age, and the number of males. In total, six articles met the eligibility criteria. The total number of patients was 399 (157 in the surgery/SRS group and 242 in the conservative treatment group). The results revealed that surgical or SRS management is a safe procedure for CMs compared with conservative treatment. Notably, the use of hemosiderin in the pre-MRI, the free of seizures parameter and the neurological deficit parameters were associated with improved outcomes in the surgical or SRS group of patients.