Porphyromonas gingivalis (P. gingivalis), a Gram-negative facultative anaerobe of the oral cavity, is associated with the onset of various adverse pregnancy outcomes. P. gingivalis is linked with the development of preeclampsia, preterm labour, spontaneous abortion, gestational diabetes, foetal growth restriction, and misconception. The unique virulence factors, surface adhesions, enzymes of P. gingivalis can directly injure and alter the morphology, microbiome the foetal and maternal tissues. P. gingivalis can even exaggerate the production of cytokines, free radicals and acute-phase proteins in the uterine compartment that increases the risk of myometrial contraction and onset of preterm labour. Although evidence confirms the presence of P. gingivalis in the amniotic fluid and placenta of women with poor pregnancy outcomes, the intricate molecular mechanisms by which P. gingivalis initiates various antenatal and postnatal maternal and foetal complications are not well explained in the literature. Therefore, the present review aims to comprehensively summarise and highlight the recent and unique molecular pathogenic mechanisms of P. gingivalis associated with adverse pregnancy outcomes.

Several tumors exhibit pH gradient reversal, with acidification of extracellular pH (pHe) and alkalinization of intracellular pH (pHi). The pH gradient reversal is evident even during the preliminary stages of tumorigenesis and is crucial for survival and propagation of tumors, irrespective of their pathology, genetics and origins. Moreover, this hallmark seems to be present ubiquitously in all malignant tumors. Based on these facts, we propose a new emerging hallmark of cancer “pH gradient reversal”. Normalizing pH gradient reversal through inhibition of various proton transporters such as Na⁺-H⁺ exchanger (NHE), Vacuolar-type H⁺-ATPase (V-ATPase), H⁺/K⁺-ATPases and carbonic anhydrases (CAs) has demonstrated substantial therapeutic benefits. Indeed, inhibition of NHE1 is now being regarded as the latest concept in cancer treatment. A recent patent deals with the utilization of cis-Urocanic acid to acidify the pHi and induce apoptosis in tumors. Another patent reports therapeutic benefit by inhibiting Lactate Dehydrogenase - 5 (LDH-5) in various cancers. Several patents have been formulated by designing drugs activated through acidic pHe providing a cancer specific action. The purpose of this review is to analyze the available literature and help design selective therapies that could be a valuable adjunct to the conventional therapies or even replace them.

Treatment planning for oral squamous cell carcinoma (OSCC) is based on the clinical TNM (Tumor, Node and Metastasis) classification. This system operates on the assumption that small tumours without clinical spread have a better prognosis than larger tumours with metastases. However, it is a well-known fact that some tumours with the same clinical staging show different growth patterns and clinical behaviour. This makes the prognosis for patients with OSCC difficult to predict on the basis of clinical staging alone. Although many histopathological characteristics of OSCC have been identified as prognostic factors, none is believed to be completely infallible. Therefore, a great need exists for more reliable prognostic markers, which will assist in treatment decisions. It is now well documented that several molecular events of significance for tumour spread, such as gain and loss of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation and initiation of angiogenesis occur at the tumour-host interface or invasive front, where the deepest and presumably most aggressive cells reside. This review describes the various molecular events and interactions, which take place in the invasive front of the OSCC, and elucidates their role as prognostic markers.

The integrity of the basal stem cell layer is critical for epithelial homoeostasis. In this paper, we review the expression of oral mucosal stem cell markers (OM-SCMs) in oral submucous fibrosis (OSF), oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF. While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF, the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness. The vacillating expression patterns of OM-SCMs confirm the role of keratins 5, 14, 19, CD44, β1-integrin, p63, sex-determining region Y box (SOX2), octamer-binding transcription factor 4 (Oct-4), c-MYC, B-cell-specific Moloney murine leukaemia virus integration site 1 (Bmi-1) and aldehyde dehydrogenase 1 (ALDH1) in OSF, OPMDs and OSCC. The downregulation of OM-SCMs in the atrophic epithelium of OSF and their upregulation during malignant transformation are illustrated with relevant literature in this review.

Epithelial-mesenchymal transition (EMT) is a critical process that occurs during the embryonic development, wound healing, organ fibrosis and the onset of malignancy. Emerging evidence suggests that the EMT is involved in the invasion and metastasis of cancers. The inflammatory reaction antecedent to fibrosis in the onset of oral submucous fibrosis (OSF) and the role of EMT in its malignant transformation indicates a hitherto unexplored involvement of EMT. This review focuses on the role of EMT markers which are regulators of the EMT mediated complex network of molecular mechanisms involved in the pathogenesis of OSF and OSCC. Further the gene enrichment analysis and pathway analysis supports the association of the upregulated and downregulated genes in various EMT regulating pathways.