Exploring the Role of E6 and E7 Oncoproteins in Cervical Oncogenesis through MBD2/3-NuRD Complex Chromatin Remodeling.

BACKGROUND: Cervical cancer is among the highest-ranking types of cancer worldwide, with human papillomavirus (HPV) as the agent driving the malignant process. One aspect of the infection's evolution is given by epigenetic modifications, mainly DNA methylation and chromatin alteration. These processes are guided by several chromatin remodeling complexes, including NuRD. The purpose of this study was to evaluate the genome-wide binding patterns of the NuRD complex components (MBD2 and MBD3) in the presence of active HPV16 E6 and E7 oncogenes and to determine the potential of identified genes through an experimental model to differentiate between cervical precursor lesions, with the aim of establishing their utility as biomarkers. METHODS: The experimental model was built using the CaSki cell line and shRNA for E6 and E7 HPV16 silencing, ChIP-seq, qRT-PCR, and Western blot analyses. Selected genes' expression was also assessed in patients. RESULTS: Several genes have been identified to exhibit altered transcriptional activity due to the influence of HPV16 E6/E7 viral oncogenes acting through the MBD2/MBD3 NuRD complex, linking them to viral infection and cervical oncogenesis. CONCLUSIONS: The impacted genes primarily play roles in governing gene transcription, mRNA processing, and regulation of translation. Understanding these mechanisms offers valuable insights into the process of HPV-induced oncogenesis.

A Narrative Review Discussing the Obstetric Repercussions Due to Alterations of Personalized Bacterial Sites Developed within the Vagina, Cervix, and Endometrium.

BACKGROUND: The reproductive tract microbiota that evolved as an integrative component has been studied intensively in the last decade. As a result, novel research, clinical opportunities, and perspectives have been derived following the close investigation of this microecological environment. This has paved the way for an update to and improvement of the management strategies and therapeutic approaches. However, obscurities, contradictions, and controversies arise regarding the ascension route from the vagina to the endometrium via the cervix, with finality in adverse obstetric outcomes. METHODS: Starting from these considerations, we aimed to gather all existing data and information from four major academic databases (PubMed, ISI Web of Knowledge, Scopus, and ScienceDirect) published in the last 13 years (2010-2023) using a controlled vocabulary and dedicated terminology to enhance the coverage, identification, and sorting of potentially eligible studies. RESULTS: Despite the high number of returned entries (n = 804), only a slight percentage (2.73%) of all manuscripts were deemed eligible following two rounds of evaluation. Cumulatively, a low level of Lactobacillus spp. and of other core microbiota members is mandatory, with a possible eubiosis-to-dysbiosis transition leading to an impairment of metabolic and endocrine network homeostasis. This transposes into a change in the pro-inflammatory landscape and activation of signaling pathways due to activity exerted by the bacterial lipopolysaccharides (LPSs)/endotoxins that further reflect a high risk of miscarriage in various stages. While the presence of some pathogenic entities may be suggestive of an adverse obstetric predisposition, there are still pros and cons of the role of specific strains, as only the vagina and cervix have been targeted as opposed to the endometrium, which recently started to be viewed as the key player in the vagina-cervix-endometrium route. Consequently, based on an individual's profile, diet, and regime, antibiotics and probiotics might be practical or not. CONCLUSIONS: Resident bacteria have a dual facet and are beneficial for women's health, but, at the same time, relaying on the abundance, richness, and evenness that are definitory indexes standing as intermediaries of a miscarriage.

A Narrative Review Discussing Vasectomy-Related Impact upon the Status of Oxidative Stress and Inflammation Biomarkers and Semen Microbiota.

BACKGROUND: Male contraceptive approaches besides tubal sterilization involve vasectomy and represent the method of choice among midlife men in developing countries thanks to many advantages. However, the subsidiary consequences of this intervention are insufficiently explored since the involved mechanisms may offer insight into a much more complex picture. METHODS: Thus, in this manuscript, we aimed to reunite all available data by searching three separate academic database(s) (PubMed, Web of Knowledge, and Scopus) published in the past two decades by covering the interval 2000-2023 and using a predefined set of keywords and strings involving "oxidative stress" (OS), "inflammation", and "semen microbiota" in combination with "humans", "rats", and "mice". RESULTS: By following all evidence that fits in the pre-, post-, and vasectomy reversal (VR) stages, we identified a total of n = 210 studies from which only n = 21 were finally included following two procedures of eligibility evaluation. CONCLUSIONS: The topic surrounding this intricate landscape has created debate since the current evidence is contradictory, limited, or does not exist. Starting from this consideration, we argue that further research is mandatory to decipher how a vasectomy might disturb homeostasis.

An Unusual Case of Urachal Cyst Misdiagnosed as a Paraovarian Cyst: Ultrasound Assessment and Differential Diagnosis.

The urachus is an embryologic remnant of the cloaca that usually degenerates after birth, resulting from the obliteration of the allantois, whose role is to connect the bladder to the umbilicus. Incomplete removal of the lumen may give rise to different malformations of the median umbilical ligament after birth. Although in the pediatric population urachus are common, most cases are asymptomatic and may go unrecognized until adulthood and give rise to cysts, rarely reported in the literature. Thus, in this manuscript we present the circumstances of a 43-year-old Romanian woman showing hypogastric pain of moderate intensity for three weeks, radiation in the left lower limb, menstrual cycle abnormalities, and dysmenorrhea. Based on the initial examinations, a paraovarian cyst measuring 80 mm was noted. Through the subsequent magnetic resonance imaging (MRI) conducted, a hypoechoic mass was detected, and the patient underwent a tumorectomy and partial cystectomy. A 9.7/7.5-cm tumor was excised, and the anatomopathological result was urachal mucinous cystadenoma. It came to our attention that relatively scarce data were found in the literature, with only seven studies with the diagnosis of the urachal cyst.

Polymorphism of clinical manifestation of HPV infection in the genital mucosa - 3-year retrospective study.

BACKGROUND: Human papillomaviruses (HPVs) are associated with a wide variety of cutaneous and mucosal infections and with malignancies in humans. More than 100 HPV types have been identified, some of which have affinity for skin and others for mucosal sites. AIM: The purpose of this study came from our desire to support the "Stop Cervical Cancer" campaign, adopted as "Cervical Cancer Removed as a Public Health Problem", following the World Health Organization (WHO) initiative in 2019-2020. At European level, cervical cancer mortality has fallen by more than 30% over the past 30 years, through coherent, consistent and comprehensive prevention programs based on accurate and consistent public information. Romania is in an unfavorable situation with regard to incidence (32.8 new cases∕100 000 women) and cervical cancer mortality (10.9 deaths∕100 000 women). Free Babes-Papanicolau (Pap) testing for early detection of cervical cancer was valid this year until March. PATIENTS, MATERIALS AND METHODS: The study runs over a period of three years, between 2016-2018, in the "Elena Doamna" Hospital of Obstetrics and Gynecology, Iasi, Romania. Of the 8500 patients hospitalized for various diseases (ovarian cysts, uterine fibroids, endometriosis, abnormal vaginal bleeding, dysmenorrhea, ectopic pregnancies, placenta praevia, spontaneous abortions and on demand, benign, malignant tumors), only 382 were present in the ambulatory for Pap test. For the other conditions, Pap test denied because the patients did not want this but to solve the condition for which they presented themselves. RESULTS: We retrospectively review 382 Pap tests of patients who presented themselves in the Ambulatory Service of the Hospital both at the advice of the gynecologist and due to the program initiated by the WHO and supported by the Department of Public Health, Iasi: "Cervical cancer can be eliminated as a problem of public health". Lesions equal to or worse than high-grade squamous intraepithelial lesion (HSIL) equivalate with high-grade lesions including HSIL (cervical intraepithelial neoplasia - CIN1, CIN2). Endometrial lesions were excluded from the study. As seen of this campaign, the number of patients has increased in 2018 (242 cases), compared to 46 cases in 2017 and 94 cases in 2016. CONCLUSIONS: Our study demonstrated that 35% (7/20) of HSIL-confirmed biopsies previously had negative HPV assays. Despite the previous negative HPV tests, a wide variety of HPV genotypes has been detected in most biopsies. In our case, we frequently identified the HPV 59 and 45 strains, 51 cases with HSIL lesions presented a first positive HPV test, 13 cases with low-grade squamous intraepithelial lesion (LSIL) showed three negative HPV tests. Prevention plays an important role in reducing the incidence of cervical cancer cases. The Pap test is now considered the primary prevention method, but consecutive vaccination significantly increases protection against high-risk HPV strains. Education plays an important role in the prophylaxis of HPV infection and cancer. It should be instituted in schools, from puberty age through partnerships or government programs with public health directorates and university hospitals or using European funds.