Back to basics in COVID-19: Antigens and antibodies-Completing the puzzle.

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.

Detection of carbapenemase producers by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS).

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.

Merkel cell polyomavirus infection in childhood: current advances and perspectives.

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.

Four historic legends in human papillomaviruses research.

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.

Fighting against human papillomavirus: the 25-year old contribution of the University of Crete School of Medicine.

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.

HPV-associated lung cancers: an international pooled analysis.

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.

Genetic diversity of the KCNE1 gene and susceptibility to postoperative atrial fibrillation.

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.

Expression of p53 family genes in urinary bladder cancer: correlation with disease aggressiveness and recurrence.

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.

Gene set enrichment analysis of the NF-κB/Snail/YY1/RKIP circuitry in multiple myeloma.

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.

Detection of human papillomavirus (HPV) DNA prevalence and p53 codon 72 (Arg72Pro) polymorphism in prostate cancer in a Greek group of patients.

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.

Expression profile of CYP1A1 and CYP1B1 enzymes in endometrial tumors.

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.

Detection and genotype analysis of human papillomavirus in non-small cell lung cancer patients.

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.

The parallel lives of pandemics: COVID­19 and obesity.

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.

Genes encoding γ­glutamyl­transpeptidases in the allicin biosynthetic pathway in garlic (Allium sativum).

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.

Neurobiology of bruxism: The impact of stress (Review).

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.

A mid­pandemic night's dream: Melatonin, from harbinger of anti­inflammation to mitochondrial savior in acute and long COVID­19 (Review).

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.

Precision medicine for respiratory diseases: A current viewpoint.

In the realm of respiratory illnesses, despite the immense costs and efforts invested in diagnosis and treatment, numerous patients with chronic respiratory conditions or malignancies do not respond well to existing therapies. Delayed diagnoses and inadequate treatments contribute to these challenges, along with adverse reactions or treatment limitations due to side-effects. However, recent advancements in understanding respiratory diseases have paved the way for personalized medical treatments, considering individual genetic, molecular and environmental factors. Precision medicine, which accommodates individual differences in disease susceptibility and response to treatments, aims to improve patient care by aligning medical research with tailored therapies. Innovative technologies, such as genomic sequencing and biomarker identification contribute to this approach, allowing for customized treatments and the identification of effective therapies. Additionally, the application of precision medicine in lung cancer treatment exemplifies the forefront of individualized care within respiratory medicine. Several studies have explored the role of precision medicine in managing respiratory infectious diseases, asthma and idiopathic pulmonary fibrosis, aiming to categorize diseases more accurately and design targeted therapies. The ultimate goal is to enhance treatment effectiveness, minimize adverse events, and shift towards a patient-centered approach to managing respiratory conditions. Despite limitations, precision medicine holds promise for improving patient outcomes and emphasizing personalized care in respiratory medicine.

Management of intracranial cavernous malformations using conservative vs. surgical and/or radiosurgical treatment: A systematic review and meta­analysis.

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.

Exploring the pathogenetic mechanisms of Mycoplasmapneumoniae (Review).

Mycoplasmas, the smallest self-replicating prokaryotes without a cell wall, are the most prevalent and extensively studied species in humans. They significantly contribute to chronic respiratory tract illnesses and pneumonia, with children and adolescents being particularly vulnerable. Mycoplasma pneumoniae (M. pneumoniae) infections typically tend to be self-limiting and mild but can progress to severe or even life-threatening conditions in certain individuals. Extrapulmonary effects often occur without pneumonia, and both intrapulmonary and extrapulmonary complications operate through separate pathological mechanisms. The indirect immune-mediated damage of the immune system, vascular blockages brought on by vasculitis or thrombosis and direct harm from invasion or locally induced inflammatory cytokines are potential causes of extrapulmonary manifestations due to M. pneumoniae. Proteins associated with adhesion serve as the primary factor crucial for the pathogenicity of M. pneumoniae, relying on a specialized polarized terminal attachment organelle. The type and density of these host receptors significantly impact the adhesion and movement of M. pneumoniae, subsequently influencing the pathogenic mechanism and infection outcomes. Adjacent proteins are crucial for the proper assembly of the attachment organelle, with variations in the genetic domains of P1, P40 and P90 surfaces contributing to the variability of clinical symptoms and offering new avenues for developing vaccines against M. pneumoniae infections. M. pneumoniae causes oxidative stress within respiratory tract epithelial cells by adhering to host cells and releasing hydrogen peroxide and superoxide radicals. This oxidative stress enhances the vulnerability of host cells to harm induced by oxygen molecules. The lack of superoxide dismutase and catalase of bacteria allows it to hinder the catalase activity of the host cell, leading to the reduced breakdown of peroxides. Lung macrophages play a significant role in managing M. pneumoniae infection, identifying it via Toll-like receptor 2 and initiating the myeloid differentiation primary response gene 88-nuclear factor κΒ signaling cascade. However, the precise mechanisms enabling M. pneumoniae to evade intracellular host defenses remain unknown, necessitating further exploration of the pathways involved in intracellular survival. The present comprehensive review delves into the pathogenesis of M. pneumoniae infection within the pulmonary system and into extrapulmonary areas, outlining its impact.