As the leading cause of neonatal morbidity and mortality, preterm birth is recognized as a major public health concern around the world. The purpose of this review is to analyze the connection between infections and premature birth. Spontaneous preterm birth is commonly associated with intrauterine infection/inflammation. The overproduction of prostaglandins caused by the inflammation associated with an infection could lead to uterine contractions, contributing to preterm delivery. Many pathogens, particularly Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Gardnerella vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Actinomyces, Candida spp., and Streptococcus spp. have been related with premature delivery, chorioamnionitis, and sepsis of the neonate. Further research regarding the prevention of preterm delivery is required in order to develop effective preventive methods with the aim of reducing neonatal morbidity.

Cancer cells acquire unique secretome compositions that contribute to tumor development and metastasis. The aim of our study was to elucidate the biological processes involved in cervical cancer, by performing a proteomic analysis of the secretome from the following informative cervical cell lines: SiHa (HPV16+), HeLa (HPV18+), C33A (HPV−), and HCK1T (normal). Proteins were analyzed by 2D gel electrophoresis coupled to MALDI-TOF-MS. Enrichment of secreted proteins with characteristic profiles for each cell line was followed by the identification of differentially expressed proteins. Particularly, transforming growth factor-beta-induced protein ig-h3 (Beta ig-h3) and peroxiredoxin-2 (PRDX2) overexpression in the secretome of cancer cell lines was detected and confirmed by Western blot. Bioinformatics analysis identified the transcription factor NRF2 as a regulator of differentially expressed proteins in the cervical cancer secretome. NRF2 levels were measured by both Western blot and Multiple Reaction Monitoring (MRM) in the total cell extract of the four cell lines. NRF2 was upregulated in SiHa and C33A compared to HCK1T. In conclusion, the secreted proteins identified in cervical cancer cell lines indicate that aberrant NRF2-mediated oxidative stress response (OSR) is a prominent feature of cervical carcinogenesis.

Background: Both HPV-positive and -negative cervical cancers are primarily associated with features of cell cycle and cytoskeletal disruption; however, the actual biological processes affected remain elusive. To this end, we systematically characterized the intracellular proteomic profiles of four distinct and informative cervical cell lines. Materials and Methods: Cell extracts from a normal cervical (HCK1T) and three cervical cancer cell lines, one HPV-negative (C33A), and two HPV-positive, SiHa (HPV16+) and HeLa (HPV18+), were analyzed by 2-dimensional electrophoresis and differentially expressed proteins were identified by MALDI-TOF mass spectrometry, while differential expression was confirmed by western blot analysis. Results: In total, 113 proteins were found differentially expressed between the normal and the cervical cancer lines. Bioinformatics analysis revealed the actin cytoskeleton signaling pathway to be significantly affected, while up-regulation of cofilin-1, an actin depolymerizing factor, was documented and further validated by western blotting. Furthermore, two-way comparisons among the four cell lines, revealed a set of 18 informative differentially expressed proteins. Conclusion: These novel identified proteins provide the impetus for further functional studies to dissect the mechanisms operating in the two distinct pathways of cervical carcinogenesis.

Gestational diabetes mellitus (GDM) occurs in approximately 9–25% of pregnancies and, if left undiagnosed or inadequately controlled, can lead to adverse outcomes for both the mother and the fetus, short and long term. GDM is characterized by glucose intolerance with onset or first recognition during pregnancy and is a multifactorial condition with a pathophysiology that remains incompletely understood. It is strongly associated with a chronic low-grade inflammatory state that contributes to insulin resistance, a hallmark of GDM pathogenesis. Among the fundamental pro-inflammatory cytokines implicated in this process, TNF-α and IL-6 play central roles. TNF-α is a cytokine primarily secreted by activated macrophages, as well as by adipocytes in the context of obesity. Many studies have shown that its levels are elevated in pregnant women with GDM compared to normoglycemic pregnant individuals. IL-6 is another pro-inflammatory cytokine secreted by immune cells, adipose tissue, and the placenta. It is found in higher concentrations in the maternal circulation during pregnancies complicated by GDM. Both TNF-α and IL-6 act synergistically to perpetuate a pro-inflammatory intrauterine environment. Their combined effects exacerbate insulin resistance and may impair pancreatic β-cell compensation during pregnancy, facilitating the onset of GDM in genetically or metabolically susceptible individuals. Recent research has identified various maternal serum biomarkers, such as TNF-α and IL-6, that may hold promise for the early detection of GDM. The aim of our study is to evaluate whether TNF-α and IL-6 can be used as diagnostic tools for the early diagnosis of GDM, allowing for timely intervention and reducing the risk of associated maternal and fetal complications.

Background: Oncogenic infection by HPV, eventually leads to cervical carcinogenesis, associated by deregulation of specific pathways and protein expression at the intracellular and secretome level. Thus, secretome analysis can elucidate the biological mechanisms contributing to cervical cancer. In the present study we systematically analyzed its constitution in four cervical cell lines employing a highly sensitive proteomic technology coupled with bioinformatics analysis. Materials and Methods: LC/MS-MS proteomics and bioinformatics analysis were performed in the secretome of four informative cervical cell lines SiHa (HPV16⁺), HeLa (HPV18⁺), C33A (HPV⁻) and HCK1T (normal). Results: The proteomic pattern of each cancer cell line compared to HCK1T was identified and a detailed bioinformatics analysis disclosed inhibition of matrix metalloproteases in cancer cell lines. This prediction was further confirmed via zymography for MMP-2 and MMP-9, western blot analysis for ADAM10 and by MRM for TIMP1. The differential expression of important secreted proteins such as CATD, FUCA1 and SOD2 was also confirmed by western blot analysis. MRM-targeted proteomics analysis confirmed the differential expression of CATD, CATB, SOD2, QPCT and NEU1. Conclusion: High resolution proteomics analysis of cervical cancer secretome revealed significantly deregulated biological processes and proteins implicated in cervical carcinogenesis.

Cervical cancer incidence is tightly linked to HPV infection, and particularly virus types 16 and 18 cause the majority of cases presenting with pre-cancerous stages of cervical intraepithelial neoplasia (CIN). Structural and functional information concerning HPV proteins can offer novel insight into the mechanism(s) of cancer progression in the cervical epithelium. Recently, novel structural determinants of the interactions of viral proteins with their targets in keratinocytes have been elucidated. These exciting findings open the way for the development of targeted anti-oncogenic therapies, and may eventually allow the introduction of novel approaches for a rational cervical cancer treatment.