## 4 Discussion
The evaluation of more biochemical markers was also intended, but the delivery of some reagents and kitsfor analysis was delayed, also because of the pandemic and the restrictions. Despite that, further studies should be conducted to clarify the role of the studied biomarkers in acute and chronically inflamed pulp tissues, as results among different studies vary. Evaluations into other various biomarkers are also needed in order to help establish dental pulp condition. Precisely, a potential marker could be the anti-cyclic citrullinated peptide antibodies (anti-CPP), which was evaluated by [PERSON] et al. [43] in patients with periodontal disease, another major oral condition, and in patients with periodontal disease and rheumatoid arthritis. The results of their study did not show a correlation with the clinical signs of pathology, but citrullination of proteins by the _P. gingivalis_ (present in endodontic infections) PAD enzyme could lead to local inflammation in the infected endodontic space [44]. More studies in the field are needed, and an evaluation of anti-CPP antibodies in dental pulp should be considered as a probable diagnostic marker in the assessment of the inflammatory condition of the pulp. A rapid, more intense case of pulp inflammation or long-term pulpitis can lead to localized odontoblast death. TGF-\(\beta\) released from the dentine matrix after demineralization is capable of signaling what may lead to the differentiation of stem cells in odontoblast-like cells [45]. Stem cells have different origins and crucial roles in reparative and regenerative procedures [46; 47]. They can be undifferentiated mesenchymal cells from the pulp core, which are differentiated under the inductive signal of various markers (e.g., TGF-\(\beta\)), and due to their plasticity can be divided in specific cell lineages [46; 48]. They are also capable of limitless self-renewal and may have an important role in treating hard dental tissue defects after an injury, by differentiating in odontoblast-like cells and secreting reparative dentine, which will lead to pulpal healing and reparation [46]. Induced pluripotent stem cells (iPSCs) are also promising, as they can participate in the regeneration of mineralized tissues [47]. Exogenous stem cells can be placed in the pulp if severe lesions occur and irreversible damage takes place, aiming for regeneration of pulp tissue and mineralized matrix formation [47; 49]. During the inflammatory process of the dental pulp, molecular modifications precede macroscopic and microscopic inflammatory alterations; thus, early diagnoses may be established if biomarker determination could be put into practice. One attempt could be done by obtaining pulpal tissue through minimal invasive treatments, such as vital pulotomy or even partial pulotomy, if possible, and testing for the presence of biomarkers, the result being corroborated with the patient's clinical findings. We should also consider non-invasive methods for the assessment of pulpal conditions, such as dentinal fluid collections, which contain serum proteins and immunoglobulins [6; 50]. Seeking dental treatment at an early stage of inflammation and recognizing the pulp condition is compulsory to apply non-invasive/minimal invasive methods. Molecular evaluation of biomarkers associated with short-term pain caused by thermal stimulation, which can be precisely localized, can lead to reversible pulp inflammation diagnosis, which is usually treated by partial or total pulotomy, aiming for pulpal healing. A spontaneous, lingering pain to thermal stimuli related to biomarker assessment is indicative of an acute irreversible inflammation, which is usually followed by complete pullectomy. On the other hand, a dull pain with hypoexcitability on cold stimulation and marker evaluation may establish the diagnosis of chronic inflamed dental pulp, followed by pulectomy and root canal treatment.