Microbiome and cancer: from mechanistic implications in disease progression and treatment to development of novel antitumoral strategies.

Cancer is a very aggressive disease and one of mankind's most important health problems, causing numerous deaths each year. Its etiology is complex, including genetic, gender-related, infectious diseases, dysbiosis, immunological imbalances, lifestyle, including dietary factors, pollution etc. Cancer patients also become immunosuppressed, frequently as side effects of chemotherapy and radiotherapy, and prone to infections, which further promote the proliferation of tumor cells. In recent decades, the role and importance of the microbiota in cancer has become a hot spot in human biology research, bringing together oncology and human microbiology. In addition to their roles in the etiology of different cancers, microorganisms interact with tumor cells and may be involved in modulating their response to treatment and in the toxicity of anti-tumor therapies. In this review, we present an update on the roles of microbiota in cancer with a focus on interference with anticancer treatments and anticancer potential.

Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship.

Testicular germ cell tumors (TGCTs) are the most common type of testicular cancer, with a particularly high incidence in the 15-45-year age category. Although highly treatable, resistance to therapy sometimes occurs, with devastating consequences for the patients. Additionally, the young age at diagnosis and the treatment itself pose a great threat to patients' fertility. Despite extensive research concerning genetic and environmental risk factors, little is known about TGCT etiology. However, epigenetics has recently come into the spotlight as a major factor in TGCT initiation, progression, and even resistance to treatment. As such, recent studies have been focusing on epigenetic mechanisms, which have revealed their potential in the development of novel, non-invasive biomarkers. As the most studied epigenetic mechanism, DNA methylation was the first revelation in this particular field, and it continues to be a main target of investigations as research into its association with TGCT has contributed to a better understanding of this type of cancer and constantly reveals novel aspects that can be exploited through clinical applications. In addition to biomarker development, DNA methylation holds potential for developing novel treatments based on DNA methyltransferase inhibitors (DNMTis) and may even be of interest for fertility management in cancer survivors. This manuscript is structured as a literature review, which comprehensively explores the pivotal role of DNA methylation in the pathogenesis, progression, and treatment resistance of TGCTs.

COVID-19 and flu vaccination in Romania, post pandemic lessons in healthcare workers and general population.

BACKGROUND: Influenza and corona viruses generate vaccine preventable diseases and have pandemic potential, frequently dramatic. A co-infection with these viruses, may be a new worldwide threat, researchers name it flurona. The aim of our study is to assess flu and COVID-19 Romanian vaccination for 2022-2023 season and the factor associated with higher odds to receive flu and COVID-19 vaccine. METHODS: An analytical cross-sectional observational survey was conducted in the general population; a self-administered questionnaire was used. RESULTS: 1056 responders were analyzed, mean age 32.08 ±13.36 years (limits:18-76), majority, 880 (83.33%), from urban areas, 608 (57.58%), high school graduated, 400 (37.88%) parents. More than half of the responders were healthcare workers, 582 (55.11%), also considered study population. In the study group, 796 (73.37%) responders consider flurona vaccination useful; and 872 (82.57%) responders consider that no sanctions are needed for not flurona vaccinating. In the 2022-2023 season, 162 (15.34%) responders vaccinated against the flu and 300 (28.41%) against COVID-19. The factor associated with higher odds to receive flu and COVID-19 vaccine was the habit of flu vaccination: for flu (OR = 58.43; 95% CI: (34.95-97.67)) and for COVID-19 (OR = 1.67; 95% CI: (1.21-2.31)). Other factors such as having university degree (OR = 1.46; 95% CI: (1.08-1.98)) and being a healthcare worker, (OR = 1.41; 95% CI: (1.07-1.87)) were influencing factors only for adult COVID-19 vaccination in the 2022-2023 season. In the parents' group, in 2022-2023 season, only 48 (12%) vaccinated their children against the flu and 68 (17%) against COVID-19, mostly parents that vaccinated themselves, p<0.001. In the 2022-2023 season, there were only 82 (7.65%) responders vaccinated against both diseases. Logistic regression analysis showed that no factor analyzed influenced the flurona vaccinated parent's decision to vaccinate their children for flu and for COVID-19. CONCLUSIONS: In the season 2022-2023, in Romania, the vaccination against flu and COVOD-19 is low, in adults and children as well. More efforts must be done to increase flurona vaccination, public health educational programs are strongly needed. Children, that are at greater risk when co-infecting with these viruses, must be vaccinated, school vaccination programs should be considered.

H3 histone methylation landscape in male urogenital cancers: from molecular mechanisms to epigenetic biomarkers and therapeutic targets.

During the last decades, male urogenital cancers (including prostate, renal, bladder and testicular cancers) have become one of the most frequently encountered malignancies affecting all ages. While their great variety has promoted the development of various diagnosis, treatment and monitoring strategies, some aspects such as the common involvement of epigenetic mechanisms are still not elucidated. Epigenetic processes have come into the spotlight in the past years as important players in the initiation and progression of tumors, leading to a plethora of studies highlighting their potential as biomarkers for diagnosis, staging, prognosis, and even as therapeutic targets. Thus, fostering research on the various epigenetic mechanisms and their roles in cancer remains a priority for the scientific community. This review focuses on one of the main epigenetic mechanisms, namely, the methylation of the histone H3 at various sites and its involvement in male urogenital cancers. This histone modification presents a great interest due to its modulatory effect on gene expression, leading either to activation (e.g., H3K4me3, H3K36me3) or repression (e.g., H3K27me3, H3K9me3). In the last few years, growing evidence has demonstrated the aberrant expression of enzymes that methylate/demethylate histone H3 in cancer and inflammatory diseases, that might contribute to the initiation and progression of such disorders. We highlight how these particular epigenetic modifications are emerging as potential diagnostic and prognostic biomarkers or targets for the treatment of urogenital cancers.

Ageing People Living with HIV/AIDS, PLWHA; More Dental Challenges; the Romanian Dental Professional's Point of View.

BACKGROUND: In Romania, HIV (human immunodeficiency virus) and AIDS (acquired immunodeficiency syndrome) were first acknowledged in 1989. Getting older with HIV/AIDS is now possible due to antiretroviral treatment, but it can bring dental problems due to HIV itself or to the reluctance of dental professionals to treat dental problems. Our study aims to assess the attitudes, knowledge, and practices of Romanian dental professionals regarding aging PLWHA. METHODS: An analytical cross-sectional observational survey based on a self-administered questionnaire was conducted for Romanian dental professionals from October 2022 to January 2023. RESULTS: The responders' group profile was as follows: a mean age of 39.09 ± 0.36 years (limit: 19-75), a majority of 991 (90.01%) from urban dental offices, and 364 (33.06%) with more than twenty years' experience. A total of 517 (46.95%) responders had an unprofessional attitude and declared that, if possible, they would avoid taking part in performing dental treatments for people living with HIV/AIDS (PLWHA). There were 89 (8.08%) dental professionals that refused to work with PLWHA. Only 363 (32.97%) had worked with one previously. The dental professionals in rural areas refused PLWHA more frequently: 20% (N = 22) of rural dental professionals vs. 6.76% (N = 67) of urban dental professionals refused to work with PLWHA (OR = 0.30; 95% CI: 0.16-.56). The logistic regression applied for the 1101 responders revealed after stepwise selection that the most influential factor for their refusal to work with PLWHA in our study group was being previously exposed to HIV during dental practice (OR = 14.45; 95% CI: 8.55- 24.42; p = 0.000). CONCLUSIONS: Dental educators and health care planners should promote the knowledge of prophylaxis and positive attitudes towards the treatment of PLWHA. Successful resolution of these concerns is time consuming and expensive but necessary if dentists are to satisfy their professional obligations to HIV/AIDS patients.

Common themes in antimicrobial and anticancer drug resistance.

Antimicrobial and anticancer drug resistance represent two of the main global challenges for the public health, requiring immediate practical solutions. In line with this, we need a better understanding of the origins of drug resistance in prokaryotic and eukaryotic cells and the evolutionary processes leading to the occurrence of adaptive phenotypes in response to the selective pressure of therapeutic agents. The purpose of this paper is to present some of the analogies between the antimicrobial and anticancer drug resistance. Antimicrobial and anticancer drugs share common targets and mechanisms of action as well as similar mechanisms of resistance (e.g., increased drug efflux, drug inactivation, target alteration, persister cells' selection, protection of bacterial communities/malignant tissue by an extracellular matrix, etc.). Both individual and collective stress responses triggered by the chemotherapeutic agent involving complex intercellular communication processes, as well as with the surrounding microenvironment, will be considered. The common themes in antimicrobial and anticancer drug resistance recommend the utility of bacterial experimental models for unraveling the mechanisms that facilitate the evolution and adaptation of malignant cells to antineoplastic drugs.

Epigenetics and Testicular Cancer: Bridging the Gap Between Fundamental Biology and Patient Care.

Testicular cancer is the most common solid tumor affecting young males. Most testicular cancers are testicular germ cell tumors (TGCTs), which are divided into seminomas (SGCTs) and non-seminomatous testicular germ cell tumors (NSGCTs). During their development, primordial germ cells (PGCs) undergo epigenetic modifications and any disturbances in their pattern might lead to cancer development. The present study provides a comprehensive review of the epigenetic mechanisms-DNA methylation, histone post-translational modifications, bivalent marks, non-coding RNA-associated with TGCT susceptibility, initiation, progression and response to chemotherapy. Another important purpose of this review is to highlight the recent investigations regarding the identification and development of epigenetic biomarkers as powerful tools for the diagnostic, prognostic and especially for epigenetic-based therapy.

Advances in the Rapid Diagnostic of Viral Respiratory Tract Infections.

Viral infections are a significant public health problem, primarily due to their high transmission rate, various pathological manifestations, ranging from mild to severe symptoms and subclinical onset. Laboratory diagnostic tests for infectious diseases, with a short enough turnaround time, are promising tools to improve patient care, antiviral therapeutic decisions, and infection prevention. Numerous microbiological molecular and serological diagnostic testing devices have been developed and authorised as benchtop systems, and only a few as rapid miniaturised, fully automated, portable digital platforms. Their successful implementation in virology relies on their performance and impact on patient management. This review describes the current progress and perspectives in developing micro- and nanotechnology-based solutions for rapidly detecting human viral respiratory infectious diseases. It provides a nonexhaustive overview of currently commercially available and under-study diagnostic testing methods and discusses the sampling and viral genetic trends as preanalytical components influencing the results. We describe the clinical performance of tests, focusing on alternatives such as microfluidics-, biosensors-, Internet-of-Things (IoT)-based devices for rapid and accurate viral loads and immunological responses detection. The conclusions highlight the potential impact of the newly developed devices on laboratory diagnostic and clinical outcomes.

Microbiome, Mycobiome and Related Metabolites Alterations in Patients with Metabolic Syndrome-A Pilot Study.

Metabolic syndrome (MetSyn) has a rapidly growing worldwide prevalence, affecting over 1 billion people. MetSyn is clustering many pathological conditions, which, untreated, could increase the risk and often lead to more severe metabolic defects such as type 2 diabetes and non-alcoholic fatty liver disease. Many data demonstrate the complex role of gut microbiota in the host metabolism, and hence, deciphering the microbiome patterns linked to MetSyn could enable us for novel diagnosis and monitoring markers and for better disease management. Moreover, interventions designed to alter patient microbiome composition may help prevent or decrease morbidity linked with MetSyn. However, the microbiome composition is largely different across geographically distinct populations. Our study investigated the microbiota and mycobiome patterns in Romanian metabolic syndrome patients. We also correlated the identified microbiome-mycobiome patterns with levels of metabolites important for host health such as short chain fatty acids, organic acids, and taurine. We found that MetSyn patients are harboring a microbiome enriched in Enterobacteriaceae, Turicibacter sp., Clostridium coccoides, and Clostridium leptum, while beneficial taxa such as Butyricicoccus sp., Akkermansia muciniphila, and Faecalibacterium prausnitzii were decreased. These microbiome changes were correlated with lower butyrate levels and increased succinate. In terms of mycobiome signatures, MetSyn was associated with a high abundance of Saccharomyces and Aspergillus species. Our data are the first reported on a Romanian population and confirming that the pathogenesis of MetSyn is closely related to gut microbiome and homeostasis.

Antiviral Immunity in SARS-CoV-2 Infection: From Protective to Deleterious Responses.

After two previous episodes, in 2002 and 2012, when two highly pathogenic coronaviruses (SARS, MERS) with a zoonotic origin emerged in humans and caused fatal respiratory illness, we are today experiencing the COVID-19 pandemic produced by SARS-CoV-2. The main question of the year 2021 is if naturally- or artificially-acquired active immunity will be effective against the evolving SARS-CoV-2 variants. This review starts with the presentation of the two compartments of antiviral immunity-humoral and cellular, innate and adaptive-underlining how the involved cellular and molecular actors are intrinsically connected in the development of the immune response in SARS-CoV-2 infection. Then, the SARS-CoV-2 immunopathology, as well as the derived diagnosis and therapeutic approaches, will be discussed.

DNA methyltransferase inhibitors modulate histone methylation: epigenetic crosstalk between H3K4me3 and DNA methylation during sperm differentiation.

The process of cytodifferentiation in spermatogenesis is governed by a unique genetic and molecular programme. In this context, accurate 'tuning' of the regulatory mechanisms involved in germ cells differentiation is required, as any error could have dramatic consequences on species survival and maintenance. To study the processes that govern the spatial-temporal expression of genes, as well as analyse transmission of epigenetic information to descendants, an integrated approach of genetics, biochemistry and cytology data is necessary. As information in the literature on interplay between DNA methylation and histone H3 lysine 4 trimethylation (H3K4me3) in the advanced stages of murine spermatogenesis is still scarce, we investigated the effect of a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, at the cytological level using immunocytochemistry methodology. Our results revealed a particular distribution of H3K4me3 during sperm cell differentiation and highlighted an important role for regulation of DNA methylation in controlling histone methylation and chromatin remodelling during spermatogenesis.

Histone hyperacetylation and DNA methylation interplay during murine spermatogenesis.

Male germ cell development is a critical period during which epigenetic patterns are established and maintained. The progression from diploid spermatogonia to haploid spermatozoa involves the incorporation of testis-specific histone variants, mitotic and meiotic divisions, haploid gene expression, histone-protamine transitions and massive epigenetic reprogramming. Understanding the protein players and the epigenetic mark network involved in the setting of the epigenetic programme in spermatogenesis is an exciting new clue in the field of reproductive biology with translational outcomes. As information in the existing literature regarding cross-talk between DNA methylation and histone hyperacetylation in the advanced stages of murine spermatogenesis is still scarce and controversial we have investigated the effect of a DNA-methyltransferase inhibitor, 5-aza-2'-deoxycytidine, at the cytological and molecular level (by transmission electron microscopy, immunocytochemistry and immunoprecipitation methods). Our results revealed an important role for regulation of DNA methylation in controlling histone hyperacetylation and chromatin remodelling during spermatogenesis.

Suspicions of titanium allergic reaction influencing the prosthetic solution in a rare case of implant "flowering".

The aim of this paper is to eliminate suspicions of a titanium (Ti) allergy in a rare case of "flowered" implant in a 43-year-old female patient with metal allergies and no history of bruxism, using a histological and immunohistochemical (IHC) analysis to determine the phenotype of cells that participated in the immune response; also, to assess the prognosis of a future implant treatment and to highlight the psychological impact of osseointegrated implant failure caused by fracture, and the influence that the necessity to use extensive surgical procedures for reimplantation can have on the treatment solution chosen by the patient. The results of our IHC analysis did not indicate a clear response for a potential Ti allergy; still, due to psychological reasons, the patient rejected the replantation and considered the use of other restorative option, a three-unit bridge, as being the most appropriate for her. Considering her opinion and attitude, the fixed prosthetic denture assured the therapeutic success.

In vivo effects of Trichostatin A - A histone deacetylase inhibitor - On chromatin remodeling during Triturus cristatus spermatogenesis.

A major challenge in developmental biology field is to decipher the molecular mechanisms involved in cellular differentiation and to understand the processes that control and regulate genes expression. The study of nuclear molecular architecture during gametogenesis represents one approach toward deciphering the molecular organization and function of the eukaryotic chromatin. As spermatogenesis progresses, there is a widespread reorganization of the haploid genome followed by extensive DNA compaction. It is becoming increasingly evident that the dynamic composition of chromatin plays an important role in the activities of enzymes and in the processes that act upon it. As the information in the existing literature regarding the epigenetic modifications occurring in the advanced stages of spermatogenesis of crested newt is still scarce, we have investigated the effect of a Histone Deacetylase (HDAC) inhibitor, Trichostatin A (TSA), at the cytological level (by transmission electron microscopy - TEM, immunohistochemistry technique, fluorescence microscopy) and at the molecular level (AUT-PAGE and ChIP assay) on Triturus cristatus spermatogenesis. Our results have revealed an important role for regulation of histone deacetylase activity in controlling histone hyperacetylation and the replacement with sperm nuclear basic proteins during spermiogenesis.

Chromatin dynamics in Triturus cristatus oogenesis: an epigenetic approach.

Oogenesis is a critical event in the formation of female gametes, whose role in development is to transfer genomic information to the next generation. During this process, the gene expression pattern changes dramatically concomitant with genome remodelling, while genomic information is stably maintained. The aim of the present study was to investigate the chromatin architecture in newt oocytes. Using fluorescence microscopy, as well as transmission electron microscopy (TEM), immunohistochemical method and RE-ChIP assay, some peculiar aspects of chromatin and chromosome organization and evolution in crested newt oogenesis were investigated. We focussed our investigations on detection of certain epigenetic modifications (H4 hyperacetylation, H2A ubiquitinylation and cytosine methylation) at the rRNA gene (18S-5.8S-28S) promoter region. Our findings suggest that there is an involvement of some epigenetic modifications as well as of linker histone variants in chromatin architecture dynamics during crested newt oogenesis.

Molecular and ultrastructural studies of the sperm chromatin from Triturus cristatus.

The study of nuclear molecular architecture during gametogenesis represents one approach towards the deciphering of the molecular organization of eukaryotic chromatin. During spermatogenesis, chromatin undergoes several dynamic transitions, which are often associated with important changes not only in its physical conformation but even in its composition and structure. Dynamic alterations in chromatin structure mediated by postsynthetic histone modification and DNA methylation constitute a major regulatory mechanism of gene function of eukaryotes. Using transmission electron microscopy and molecular investigations, some peculiar aspects of chromatin organization and evolution in spermatogenesis of the crested newt Triturus cristatus were investigated. We focused our investigations on the dynamics of chromatin structure after treatment with TSA (a histone deacetylase inhibitor).