The pigmented lesions of the oral cavity may be endogenous or exogenous. Among the options for depigmenting these areas, laser therapy stands out for being a minimally invasive procedure. This study aims to report a clinical case of the gingival depigmentation technique using a high-power diode laser in the anterior maxillary region, for the ablation of the pigmented tissue to improve gingival aesthetics. The patient had an aesthetic complaint of the darkened aspect of the gingiva in the anterior maxillary portions. After local anesthesia, we started depigmentation with a high-power diode laser and performed ablation from the attached gingiva toward the free marginal gingiva. The patient returned after 30 and 180 days presenting healthy gingiva and absence of melanin repigmentation. Thus, we concluded that the diode laser was a good alternative for melanin depigmentation because it is a procedure with lower morbidity and satisfactory results.

Metabolites resulting from the bacterial fermentation of dietary fibers, such as short-chain fatty acids, especially butyrate, play important roles in maintaining gut health and regulating various biological effects in the skin. However, butyrate is underutilized due to its unpleasant odor. To circumvent this organoleptic unfavorable property, phenylalanine butyramide (PBA), a butyrate precursor, has been synthesized and is currently available on the market. We evaluated the inhibition of mushroom tyrosinase by butyrate and PBA through in vitro assays, finding IC50 values of 34.7 mM and 120.3 mM, respectively. Docking calculations using a homology model of human tyrosinase identified a putative binding mode of PBA into the catalytic site. The anti-aging and anti-spot efficacy of topical PBA was evaluated in a randomized, double-blind, parallel-arm, placebo-controlled clinical trial involving 43 women affected by photo-damage. The results of this study showed that PBA significantly improved skin conditions compared to the placebo and was well tolerated. Specifically, PBA demonstrated strong skin depigmenting activity on both UV and brown spots (UV: -12.7% and -9.9%, Bs: -20.8% and -17.7% after 15 and 30 days, respectively, p < 0.001). Moreover, PBA brightened and lightened the skin (ITA°: +12% and 13% after 15 and 30 days, respectively, p < 0.001). Finally, PBA significantly improved skin elasticity (Ua/Uf: +12.4% and +32.3% after 15 and 30 days, respectively, p < 0.001) and firmness (Uf: -3.2% and -14.9% after 15 and 30 days, respectively, p < 0.01).

BACKGROUND: Piebaldism is a rare autosomal dominant disorder characterized by congenital white forelock and depigmented patches, which is most commonly caused by deleterious variants in the KIT gene.
METHODS: Four KIT variants were identified in a piebaldism case series by whole-exome sequencing. Functional experiments, including in vitro minigene reporter assay and enzyme-linked immunosorbent assay, were carried out to elucidate the pathogenicity of the variants. The genotype-phenotype correlation was summarized through extensive literature reviewing.
RESULTS: All the four cases had severe piebaldism presented with typical white forelock and diffuse depigmentation on the ventral trunk and limbs. Four germline variants at the tyrosine kinase (TK) domains of the KIT gene were identified: two novel variants c.1990+1G>A (p.Pro627_Gly664delinsArg) and c.2716T>C (p.Cys906Arg), and two known variants c.1879+1G>A (p.Gly592_Pro627delinsAla) and c.1747G>A (p.Glu583Lys). Both splicing variants caused exon skipping and inframe deletions in the TK1 domain. The missense variants resided at the TK1 and TK2 domains respectively impairing PI3K/AKT and MAPK/ERK signaling pathways, the downstream of KIT. All severe cases were associated with variants in the TK domains, eliciting a major dominant-negative mechanism of the disease.
CONCLUSIONS: Our data expand the mutation spectrum of KIT, emphasized by a dominant-negative effect of variants in the critical TK domains in severe cases. We also share the experience of prenatal diagnosis and informed reproductive choices for the affected families.

Pruritus, rash, and various other forms of dermatotoxicity are the most frequent adverse events among patients with cancer receiving targeted molecular therapy and immunotherapy. Immune checkpoint inhibitors, macrophage-targeting agents, and epidermal growth factor receptor/MEK inhibitors not only exert antitumor effects but also interfere with molecular pathways essential for skin immune homeostasis. Studying cancer therapy-induced dermatotoxicity helps us identify molecular mechanisms governing skin immunity and deepen our understanding of human biology. This review summarizes new mechanistic insights emerging from the analysis of cutaneous adverse events and discusses knowledge gaps that remain to be closed by future research.

The most common aesthetic issue that affects people\'s smiles is gingival pigmentation, especially in those with high smile lines. This pigmented gingiva is thought to be naturally occurring melanin pigments that add to the gingiva\'s endogenous pigmentation. The goal of plastic periodontal surgery known as \"gingival depigmentation\" is to lighten the dark gingiva by scraping off the gingival epithelium. Gingival depigmentation has been performed with a variety of techniques, including bur abrasion, scraping, partial thickness flap, cryotherapy, electrocautery, and laser. The present case comprised a split-mouth design in which depigmentation using an electrosurgical unit and soft tissue trimming bur was used for the maxillary sections, and evaluated the difference in pain felt by the patient and healing of the surgical site between the sites treated with the electrosurgical unit and bur abrasion method. A visual analog scale (VAS) was used to quantify pain felt by the patient on the seventh day, whereas healing was assessed on the seventh day and at a one-month interval visually. The results of this study showed that the electrocautery-treated site showed better results in terms of pain experienced by the patient and also with the surgical site healing.

UNASSIGNED: Programmed death ligand 1 (PD-L1) score is an important companion diagnosis to predict the response to immunotherapy. Immunohistochemistry can accurately assess the expression of PD-L1 in routine paraffin-embedded tissue. However, whether decalcified or depigmented tissue is still accurate and can be used as a companion diagnosis is controversial. This study attempts to resolve this controversy by analyzing the effects of decalcification and depigmentation at different times on PD-L1 expression.
UNASSIGNED: Placental tissues were selected for tissue microarray, decalcification was performed according to time gradients of 6, 12, 24, 36, and 48 h, and depigmentation was performed according to time gradients of 1, 5, 15, 30, and 60 min. The intensity of PD-L1 expression at different time points was observed and quantified. Ten PD-L1-positive esophageal squamous carcinoma samples were selected for decalcification treatment, and the PD-L1. Combined Positive Score (CPS), Tumor Proportion Score (TPS) and Immunocyte Proportion Score (IPS) and the positivity rates were compared before and after decalcification.
UNASSIGNED: After the placenta was decalcified, the intensity of PD-L1 positivity diminished, and the average optical density (AOD) value decreased with the prolongation of decalcification time and decreased significantly (P<0.05) at 24 h compared with the control group, and significantly (P<0.01) at 36 and 48 h compared with the control group. The intensity of PD-L1 positivity was weakened considerably after the treatment with potassium permanganate depigmentation. In addition, the AOD value decreased significantly (P<0.01) after the depigmentation time reached 5 min compared with the control group. Ten cases of PD-L1 positive esophageal squamous carcinoma were treated with 24 h decalcification, although the PD-L1 score decreased to a certain degree (P>0.05), and the positivity rate could reach 90%. After 36 h treatment, PD-L1 scores decreased, the CPS and IPS scores decreased significantly (P<0.05), and the positive rate was only 50%.
UNASSIGNED: Potassium permanganate depigmentation significantly reduces PD-L1 expression, even for a shorter time, affecting the accuracy of the results. The accuracy of PD-L1 remained high within 24 h decalcification. The above results have certain reference value for clinical selection of immunotherapy.

UNASSIGNED: Platelet-rich fibrin (PRF) accelerates wound healing by promoting faster cicatricial tissue remodeling and excellent neovascularization. Hyaluronic acid (HA) being biocompatible, anti-inflammatory, and proangiogenic leads to improvement in the rate of wound healing.
UNASSIGNED: The aim of this study was to compare the effect of PRF membrane and 0.2% HA gel on wounds after gingival depigmentation surgery.
UNASSIGNED: This study was carried out on 30 systemically healthy individuals recruited from the pool of patients who visited the department of periodontology. After depigmentation procedure in every patient, the sites were divided into three even groups. Group A received PRF membrane and periodontal dressing, Group B received 0.2% HA gel application and periodontal dressing, and Group C served as a control group in which only periodontal dressing was placed. The individuals were evaluated for the healing index (HI) and Numerical Rating Scale (NRS) on the 3rd and 5th day. Epithelialization test (ET) was performed on the 5th day. Gingival biotype was reassessed and compared to preoperative value after 3 months. The clinical trial was expressed in terms of mean and standard deviation. Intra-group comparison and inter-group comparison were done through the Kruskal-Wallis ANOVA test. All statistical tests were performed through SPSS version 25.0 (IBM).
UNASSIGNED: The inter-group statistical analysis concerning NRS, HI, and ET showed statistically significant results in Groups A and B compared to Group C (P < 0.05), while gingival biotype showed statistically significant results in Group A compared to Groups B and C.
UNASSIGNED: The use of PRF membrane and HA gel to protect the raw wound site of depigmented gingiva proved to be an effective approach, resulting in faster healing.

Vitiligo is a common, autoimmune, depigmenting disorder of the skin. Janus Kinase inhibitors have emerged as promising topical and oral therapeutic options for vitiligo. There have been no reports of vitiligo being treated with oral Abrocitinib, a selective Janus Kinase 1 inhibitor approved for the treatment of moderate to severe atopic dermatitis. Here, we present a 61-year-old male with acrofacial vitiligo who had repigmentation plateau with twice daily tacrolimus 0.1% ointment, oral ginkgo biloba, and oral minipulse prednisone × 4 months; however, they had significant improvement after taking abrocitinib 100 mg per day for 2 months. He was able to transition topical tacrolimus twice weekly monotherapy for maintenance. This report shows that oral Janus Kinase inhibitors may be a useful option for the treatment of recalcitrant vitiligo. Results of ongoing randomized control trials are needed to determine the durability and safety of oral Janus Kinase inhibitors long-term.

The influence of a horse\'s appearance on health, sentimental and monetary value has driven the desire to understand the etiology of coat color. White markings on the coat define inclusion for multiple horse breeds, but they may disqualify a horse from registration in other breeds. In domesticated horses (Equus caballus), 35 KIT alleles are associated with or cause depigmentation and white spotting. It is a common misconception among the general public that a horse can possess only two KIT variants. To correct this misconception, we used BEAGLE 5.4-phased NGS data to identify 15 haplotypes possessing two or more KIT variants previously associated with depigmentation phenotypes. We sourced photos for 161 horses comprising 12 compound genotypes with three or more KIT variants and employed a standardized method to grade depigmentation, yielding average white scores for each unique compound genotype. We found that 7 of the 12 multi-variant haplotypes resulted in significantly more depigmentation relative to the single-variant haplotypes (ANOVA). It is clear horses can possess more than two KIT variants, and future work aims to document phenotypic variations for each compound genotype.

Traits such as shape, size, and color often influence the economic and sentimental value of a horse. Around the world, horses are bred and prized for the colors and markings that make their unique coat patterns stand out from the crowd. The underlying genetic mechanisms determining the color of a horse\'s coat can vary greatly in their complexity. For example, only two genetic markers are used to determine a horse\'s base coat color, whereas over 50 genetic variations have been discovered to cause white patterning in horses. Some of these white-causing mutations are benign and beautiful, while others have a notable impact on horse health. Negative effects range from slightly more innocuous defects, like deafness, to more pernicious defects, such as the lethal developmental defect incurred when a horse inherits two copies of the Lethal White Overo allele. In this review, we explore, in detail, the etiology of white spotting and its overall effect on the domestic horse to Spot the Pattern of these beautiful (and sometimes dangerous) white mutations.