## 4 Discussion
In addition, about a decade ago, some studies [21; 22] suggested the central role of cytokines expressed in psoriasis skin during the disease process; the interplay among them could explain most of the clinical features of psoriasis, such as the hyperproliferation of keratinocytes, increased neovascularization, and inflammation. Moreover, in 2009, [PERSON] et al. [23] hypothesized that the deranged hemostatic balance might be mainly sustained by platelet hyperactivity. In this context, a clinical relapse of this preliminary report could introduce the idea of a potential preventive intervention that could be provided to patients before psoriasis onset with the aim to modulate growth factor secretion. Some target pharmacological therapies interfering with platelet function have been proposed in the literature, which could possibly have a positive impact on skin inflammation [6] such as antiplatelet drug P2Y12 antagonists, e.g., [24]. Another example is acetylsalicylic acid (commonly referred to under the trademark Aspirin), of which effects on psoriasis are poorly investigated but promising. It has anti-inflammatory properties [25] and positive effects on various immune disorders [26]. In addition, the identification of a proper and personalized diet could influence the development and progression of psoriasis, considering that the imbalance of gut microbiota and the deficiency of vitamin D or selenium are psoriasis-associated conditions [27]. Each growth factor examined in our experiments is now discussed. First, TNF-\(\alpha\), which was released in high quantity on the first day of our experiments, is already recognized as a factor primarily involved in this pathology. It is produced by a variety of cells, such as keratinocytes, dendritic cells, and leukocytes. This implies that TNF-\(\alpha\) might be a key factor in both the initial and chronic phases of psoriasis [28]. Still, TNF-\(\alpha\) remains an enigmatic cytokine with respect to psoriasis pathogenesis because the anti-TNF biologics are not significantly effective in all psoriasis patients [29], suggesting that there may be differences in the inflammatory networks in skin lesions [30], perhaps driven by genetic background heterogeneity, with a different balance of protective and disease-associated alleles across several loci [31]. Second, VEGF [32] has a well-documented involvement in psoriasis, increasing angiogenesis and vascular permeability [33]. In addition, our data identified its increase before the onset of the symptoms. [PERSON] and [PERSON] [34] demonstrated that the psoriatic epidermis has a greater angiogenic activity associated with an increase in VEGF compared with the skin of normal subjects. Keratinocytes in lesioned skin are the major source of pro-angiogenic cytokines in psoriasis, including VEGF, TNF-\(\alpha\), and PDGF [35; 36; 37]. Moreover, VEGF increases in the plasma and serum of patients [33; 38; 39]. Third, TGF-\(\beta 1\) is considered a multipotent cytokine with a key role in many biological processes [40] among which is the pathogenesis of psoriasis [41]. To date, our data suggest a possible downregulation of TGF-\(\beta 1\) before the onset of symptoms, revealing an imbalance in the linked pathways, considering that it is involved in regulatory inflammation processes. TGF-\(\beta 1\) influences keratinocyte proliferation, activates angiogenesis, and promotes fibroblasts' production in the extracellular matrix. Data in the literature about psoriasis patients regard only studies on the established pathology, indicating an increase in this cytokine. For example, [PERSON] et al. [33] reported that the serum levels of TGF-\(\beta 1\), in addition to VEGF and NO, were significantly higher in psoriasis patients than in controls and were sensitive to changes in disease severity. Moreover, mice overexpressing human TGF-\(\beta 1\) in epidermal keratinocytes develop a skin phenotype similar to human psoriasis [42].