Cervicovaginal fluid (CVF) is a valuable source of clinical information about the female reproductive tract in both nonpregnant and pregnant women. The aim of this study is to specify the CVF proteome at different stages of cervix neoplastic transformation by label-free quantitation approach based on liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The proteome composition of CVF from 40 women of reproductive age with human papillomavirus (HPV)-associated cervix neoplastic transformation (low-grade squamous intraepithelial lesion [LSIL], high-grade squamous intraepithelial lesion [HSIL], and CANCER) was investigated. Hierarchical clustering and principal component analysis (PCA) of the proteomic data obtained by a label-free quantitation approach show the distribution of the sample set between four major clusters (no intraepithelial lesion or malignancy [NILM], LSIL, HSIL and CANCER) depending on the form of cervical lesion. Multisample ANOVA with subsequentWelch's t test resulted in 117 that changed significantly across the four clinical stages, including 27 proteins significantly changed in cervical cancer. Some of them were indicated as promising biomarkers previously (ACTN4, VTN, ANXA1, CAP1, ANXA2, and MUC5B). CVF proteomic data from the discovery stage were analyzed by the partial least squares-discriminant analysis (PLS-DA) method to build a statistical model, allowing to differentiate severe dysplasia (HSIL and CANCER) from the mild/normal stage (NILM and LSIL), and receiver operating characteristic (ROC) area under the curve (AUC) were obtained on an independent set of 33 samples. The sensitivity of the model was 77%, and the specificity was 94%; AUC was equal to 0.87. CVF proteome proved to be reflect the stage of cervical epithelium neoplastic process.
Currently, cervicitis of nonspecific etiology is one of the urgent problems of modern gynecology due to the extremely high frequency of their occurrence, a tendency to a chronic relapsing course, a negative impact on reproductive health, and the risk of developing a number of complications. The role of violations of vaginal microbiocenosis and local immune status in the development of CNC has been convincingly shown. The replacement of lactobacilli with predominantly anaerobic microorganisms (Ureaplasma, Mycoplasma, Gardnerella vaginalis, Prevotella, Peptostreptococcus spp. and Bacteroides spp.), characteristic of bacterial vaginosis, is extremely often detected in patients with CNC. Of particular importance from the point of view of clarifying the pathophysiological mechanisms of development and the development of new diagnostic and prognostic markers, as well as the personalization of CNC therapy, is the study of the cytokine status. Cervicitis and other inflammatory diseases of the lower genital tract are characterized by an increase in the expression of pro-inflammatory cytokines with simultaneous inhibition of the formation of anti-inflammatory cytokines. Significant multidirectional changes in the balance of pro- and anti-inflammatory cytokines were revealed in active and chronic sluggish cervicitis. It should be noted that, despite the variety of proposed approaches to CNC therapy, this problem is still far from being solved to date. One of the promising directions is the personalization of CNC therapy based on molecular genetic markers (polymorphisms of cytokine genes, Toll-like receptors, genes of the detoxification system). The use of such a personalized approach can significantly increase the effectiveness of CNC treatment and reduce the risk of disease recurrence.
The review article presents data on the prevalence of candidiasis of various localization against the history of coronavirus infection (COVID-19). The predisposing factors for the development and recurrence of candidiasis in patients after therapy for coronavirus infection have been analysed. Candida is one of the most common pathogens in intensive care units (ICUs), affecting 6 to 10% of patients, and some studies have reported an increasing trend in the prevalence of candidemia. The literature data that we analysed showed that the most common types of fungal infection among patients with a severe course of COVID-19 were C. albicans, then C. auris, C. glabrata, C. parapsilosis, C. tropicalis, S. cerevisiae, C. krusei and Rhodotorula spp. Candida non-albicans species, in particular C. glabrata, C. auris, were the most common causes of death. The previous treatment regimens for patients with COVID-19 included antibiotics, but at present time corticosteroids are more often used, which have an immunosuppressive effect and, accordingly, predispose to the development of candidiasis. The epithelial injury caused by SARS-CoV-2 also enables Candida to attach to the basement membrane, subsequently triggering the development of mucosal candidiasis. As the systemic and local candidiasis are conditioned by common immune mechanisms that are affected by coronavirus infection, vulvovaginal candidiasis (VVC) may recur during COVID-19 therapy. The timely diagnosis and treatment of fungal infections in patients who underwent COVID-19 are crucial for achieving a positive clinical outcome. The article provides an algorithm for the management of patients with recurrent VVC, the principles of action of antifungal drugs, their acceptability and efficacy.
The burden of persistent papillomavirus infection on public healthcare is not limited to cervical cancer (CC). At present, cervical cancer continues to be one of the most common types of cancer worldwide, although HPV also causes anogenital warts. As there is no HPV treatment available, nowadays researchers focus on the search for new therapeutic platforms, new agents for HPV-associated diseases relapse prevention after surgical treatment. Significant anticancer effects of resveratrol have been demonstrated in a variety of cancers, including breast cancer, skin cancer, lung cancer, pancreatic cancer, and stomach cancer. In CC cells, resveratrol stimulates apoptosis of cancer cells, increases expression of HPV E6 and E7, and the expression of p53 tumor suppressor protein. Protective effects on CC cells migration and invasion is achieved by inhibiting NF-κB transcription and AP-1 mediated MMP9 expression. Resveratrol demonstrates a whole range of anti-inflammatory effects, ranging from the suppression of the pro-inflammatory cytokines IL-1α, IL-1β, IL-6, IL-17 expression and inflammatory mediator prostaglandin E2, to the suppression of the formation of ROS and NO. I3K has a proven antitumor efficacy based on the molecular mechanisms of pathological cell proliferation and tumor transformation in hormone- dependent tissues, including cervical epithelial cells. Resveratrol and I3K have a wide range of studied positive therapeutic effects that can significantly reduce the likelihood of development and progression of HPV-associated lesions.
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