# Unveiling the Role of Minerals and Trace Elements of Thermal Waters in Skin Health
## 2 Minerals, Trace Elements, and Other Compounds of TSW in Skin Health
### Anions
#### 2.1.3. Bicarbonate
Furthermore, a recent ex vivo and clinical study showed that Avene TSW was able to decrease redness and reduce the overall sensitivity scale after a dermatological chemical peeling [29]. Comano thermal spring water (Comano TSW) is a low-mineralization, bicarbonate, calcium thermal spring water that has also been investigated for its anti-inflammatory and beneficial therapeutic effects on patients with psoriasis and atopic dermatitis and also in wound healing. [PERSON] et al. [30] investigated the anti-inflammatory and antiphlogistic effects of Comano TSW when applied to the skin of an albino rabbit treated with TCA 25% (a potent exfoliant) and then treated with a cold pack of Comano TSW, showing a significative decrease in inflammation compared to the control. Authors suggested that these anti-inflammatory effects were probably due to the buffer activity that bicarbonate-calcium Comano TSW has, as well as to its rehydrating effect observed in the experimental burning. [PERSON] et al. [31; 32] performed two studies to investigate the effect of CTSW in psoriatic epidermal keratinocytes. In the first assay, the results showed that CTSW was able to interfere with vascular endothelial growth factor-A isoform expression and secretion via psoriatic keratinocytes. These effects reduced all the vascular endothelial growth factor-A-mediated angiogenic, vessel-permeabilizing, and chemotactic effects. In the second study, the researchers used IL-6-hypersecreting keratinocytes isolated from six psoriatic patients and found that intracellular levels and secretion rates of IL-6 were drastically curtailed when cells were cultivated with Comano TSW. Additionally, CTSW downregulated the expression of cytokeratin-16, a marker associated with the keratinocyte psoriatic phenotype. Later studies conducted by the same research group investigated the effects of Comano TSW on cultures of epidermal keratinocytes isolated from the lesion areas of nine psoriatic patients, concluding that Comano TSW exposure significantly downregulated the intracellular levels of TNF-\(\alpha\) and also reduced the intracellular levels and secretion rates of IL-8 [33]. All these results may explain the anti-inflammatory effect of Comano TSW in psoriasis. Comano TSW has been shown to exert regenerative effects on wound healing. One in vitro study demonstrated that Comano TSW improved skin regeneration by increasing keratinocyte proliferation and migration and by favorably modulating the regenerated collagen and elastic fibers in the dermis [34]. In addition, [PERSON] et al. [35], in an ex vivo study, compared the regenerative effects of Comano TSW and a control. Human 6 mm punch skin biopsies harvested during plastic surgery sessions were injured in their central portion to induce skin loss and were cultured in either conventional medium (controls) or medium powder reconstituted with filtered Comano TSW (treated samples). At 24, 48, and 72 h, the specimens were observed following staining with hematoxylin and eosin, Picrosirius Red, orcein, and anti-proliferating cell nuclear antigen. The results showed that compared with the controls, the treated samples exhibited reduced overall cell infiltration, evidence of fibroblasts, stimulation of cell proliferation, and collagen and elastic fiber regeneration. Despite this evidence, other studies have shown that the regenerative effects cannot be attributed solely to the chemical composition, as metabolites from the Comano TSW microbiota may have a role in these properties, and a combination of the biological properties of several bacterial species within this spring water might be responsible for its regenerative effects on human skin [66; 67; 68]. [PERSON] et al. [36] conducted an observational prospective study in which patients bathed in Comano TSW alone or combined with UVB phototherapy for two weeks once a day. The results showed an improvement in quality of life and self-administered Pyoriasis Area Severity Index (SAPASI) scores in both groups.