Keratin

BACKGROUND: Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive atypia is often difficult based only on histological features. The integration of histological findings with immunohistochemistry is used in routine practice to make a diagnosis of CIS and, for this purpose, the immunohistochemical markers CK20, CD44, Ki67 and p53 are used to supplement histology. In this work, we aimed to assess CK20, CD44, Ki67 and p53 as immunohistochemical markers in patients with CIS through a systematic review and meta-analysis. MATERIALS AND METHODS: A systematic review was performed by searching electronic databases for English-language studies published from January 2010 to April 2021. Studies were considered eligible if they evaluated the CK20, CD44, Ki67 and p53 expression in CIS. RESULTS: In total, 15 references were suitable for quantitative review. The overall rate of CK20, CD44, Ki67 and p53 expression in CIS was 43%, 31%, 44%, 38%, respectively. CONCLUSIONS: Our study supports the 2014 International Society of Urologic Pathology consensus that histological assessment remains the gold standard to diagnose urothelial CIS and suggests that a very close correlation between morphological, immunohistochemical and clinical data is essential to provide the best management for patients with bladder carcinoma.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents a prevalent, long-standing hepatic condition marked by the accumulation of fat in the liver and varying degrees of fibrotic changes. Ketotifen, a mast cell stabilizer, has been proposed to modulate inflammation and fibrogenesis, but clinical evidence is limited. OBJECTIVE: To assess the effectiveness and safety of ketotifen vs vitamin E in individuals with NAFLD. The primary outcome was the change in hepatic steatosis, while the secondary outcomes included modifications in fibrosis-related indices and inflammatory biomarkers. In addition to other biochemical, anthropometric, and metabolic parameters. METHODS: In this randomized study, 60 individuals with NAFLD were allocated in a 1:1 ratio into two groups. The vitamin E group was treated with vitamin E, and the ketotifen group received ketotifen for six months. Anthropometric parameters, liver steatosis and fibrosis, lipid profile, glycemic markers, liver enzymes, matrix metalloproteinase (MMP)-9, and tumor necrosis factor (TNF)-α were measured before and after 6 months. RESULTS: Ketotifen treatment resulted in significant improvements in hepatic steatosis and disease activity compared with vitamin E, including lower steatosis and FibroScan-AST (FAST) score. Fibrosis severity was also reduced, with significant decreases in fibrosis score and fibrosis index (FIB-4) index, whereas Metabolic-Associated Steatosis Combined with Keratin-18 (MACK-3) score showed no significant between-group change. Glycemic outcomes improved significantly with ketotifen, including reductions in HOMA-IR, fasting blood glucose, and fasting insulin. Ketotifen also significantly reduced AST, TNF-α and MMP-9, and improved central adiposity measures (hip circumference, waist-stature ratio. No significant differences were observed for lipid profile, body weight, body mass index, or HbA1c. Ketotifen was generally well tolerated; drowsiness was the most common adverse event. CONCLUSION: Ketotifen exerts superior hepatoprotective, anti-inflammatory, antifibrotic, and insulin-sensitizing effects compared with vitamin E in NAFLD. These findings suggest that ketotifen may offer a prom

Remote ischemic conditioning (RIC) has been demonstrated to be effective in acute ischemic stroke, and numerous biomarkers have been investigated; however, few studies have simultaneously detected several biomarkers and observed their dynamic changes. We aimed to identify serum biomarkers whose changes are associated with RIC following stroke. This was an exploratory analysis of the RICAMIS trial, in which patients with serum samples collected were enrolled and divided into treatment groups. Serum samples were collected at admission, 3 days after randomization, and at discharge. Serum biomarkers with significantly different changes between groups were identified. Of the 25 enrolled patients, 9 patients were assigned to the RIC group, while 16 patients were assigned to the Control group. Compared with Control group, 9 serum biomarkers were found to significantlychange at admission versus 3 days after randomization, as well as at admission versus discharge in the RIC group. These included neurological biomarkers (V-type proton ATPase subunit G3 and secretogranin-3), vascular-related biomarkers (angiopoietin-related protein 6, Histone-lysine N-methyltransferase 2D, keratin type I cytoskeletal 18, and mitogen-activated protein kinase 3), inflammatory biomarkers (macrophage receptor and Nonspecific cytotoxic cell receptor protein-1), and trypsin-1. This is the first study to identify changes in serum biomarkers after RIC treatment in patients with acute ischemic stroke by quantitative proteomic analysis, which will provide the guidance for selecting target population in future clinical trials. The relationship of identified biomarkers with RIC efficacy warrants further investigation. © 2026. The Author(s).

Erratum in Int J Mol Sci. 2025 Oct 17;26(20):10115. doi: 10.3390/ijms262010115. Skin aging causes reduced hydration, elasticity, and increased wrinkles. Recent safety and compliance concerns over oral collagen supplements have increased interest in plant-based alternatives like Hibiscus sabdariffa with antioxidant and anti-aging properties. However, clinical evidence regarding its efficacy remains limited. We aimed to evaluate the effects of this plant-based collagen alternative (VC-H1, Hibiscus Enzyme Extract) supplement on skin hydration, transepidermal water loss (TEWL), desquamation, elasticity, and wrinkle reduction in photoaged individuals. A randomized, double-blind, placebo-controlled clinical trial was conducted with 98 participants (aged 35-60 years) presenting with dry skin and periorbital wrinkles. Participants randomly received 1.5 g/day of VC-H1 or placebo for 12 weeks. Skin hydration, TEWL, deep moisture, keratin index, elasticity, and wrinkle parameters were assessed at baseline, 6 weeks, and 12 weeks. VC-H1 supplementation significantly increased skin hydration, reduced the TEWL and keratin index, and improved deep moisture content for those receiving it compared with the controls. Wrinkle depth significantly decreased, and skin elasticity also improved. Those in the VC-H1 group showed greater overall improvement than those in the control group. Oral VC-H1 supplementation significantly improved skin hydration, elasticity, and wrinkle reduction, suggesting its potential as a plant-based alternative to traditional collagen supplements for skin rejuvenation.

BACKGROUND: This pilot split-mouth randomized controlled trial aimed to compare the effectiveness of an allogenic amnion-chorion membrane (ACM) in promoting clinical and histological palatal donor site wound healing to a collagen dressing (CLD). METHODS: Two palatal donor sites (right and left) of 19 participants requiring free gingival graft (FGG) procedures were randomly assigned to receive either ACM (test group) or CLD (control group). Clinical outcomes, including the size of the wound area, the degree of epithelialization, color match, bleeding condition, pain, and sensibility, were measured. Histomorphometric analyses were also performed to compare the effectiveness of the dressing in each group. Outcomes were evaluated 4, 10, 14, 21, 28, 45, and 60 days post-operatively. RESULTS: There were no significant differences in the reduction of wound area size, the degree of epithelialization, color change, pain, sensibility, thickness of the epithelium and keratin layer, number of inflammatory cells, fibroblasts and blood vessels, and density of collagen between ACM and CLD palatal donor sites during all the evaluations. CONCLUSIONS: The effectiveness of ACM in supporting wound healing at the palatal FGG donor site was comparable to that of CLD. CLINICAL TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (ID NCT03713073). The title of the trial is Clinical and Histological Outcomes of Allogenic Amnion Chorion Membrane in the Healing of Free Gingival Graft Donor Site. PLAIN LANGUAGE SUMMARY: This study looked at how well 2 different treatments help wounds heal after a free gingival graft procedure, which requires taking donor tissue from the palate. Nineteen participants had 2 areas on their palates treated: 1 with an allogenic amnion-chorion membrane (ACM) and the other with a collagen dressing. The study compared the healing process by looking at the size of the wound, the kinetics of the wound healed, the pain experienced, and the tissue's appearance. It also examined the treated sites under a microscope to assess the number of cells involved in the healing process. After evaluating the healing progress at several time points (from 4 to 60 d

BACKGROUND: Noninvasive tests (NITs) to monitor metabolic dysfunction-associated steatohepatitis (MASH) progression and response to interventions are needed because of the risks of liver biopsy. A monocytes-based diagnostic test using perilipin-2 (PLIN2) and Ras-related protein-14 (RAB14) predict the severity of MASH and fibrosis. Here we compared the performances of PLIN2 and RAB14 with cytokeratin-18 (CK18) assessed by Ella™ or M65 ELISA in predicting MASH and fibrosis resolution following bariatric surgery in a longitudinal and histologically characterized cohort of individuals with obesity. METHODS: Participants in the BRAVES randomized controlled trial underwent ultrasound-guided needle liver biopsy at baseline and 1 year after surgery. We evaluated NITs' performance using area under the receiver operating characteristic and calculated accuracy, sensitivity, and specificity based on the Youden threshold. Univariable and multivariable logistic models were used to assess the role of recorded covariates in predicting MASH and fibrosis severity, as well as resolution or improvement. RESULTS: After surgery, patients who experienced MASH improvement or resolution showed a significant decrease in PLIN2 expression as compared to those who did not, while patients with fibrosis improvement displayed an increase in RAB14. No differences were found for CK18. The diagnostic accuracy of PLIN2 and RAB14 for the prediction of MASH resolution or fibrosis improvement was superior to CK18 assessed by either Ella or M65 ELISA. CONCLUSIONS: PLIN2 and RAB14, but not CK18, are markers for monitoring improvements in MASH and fibrosis after interventions such as bariatric surgery. This may reduce or eliminate the need for frequent liver biopsies. ClinicalTrials.gov Registration Number: NCT03524365. © Association for Diagnostics & Laboratory Medicine 2024.

BACKGROUND: Keratin hydrolysates are active components used in food supplements to alleviate aging signs on skin, hair, and nails. AIMS: This randomized, double-blind, placebo-controlled study evaluates a novel keratin hydrolysate obtained from poultry feathers. This feather keratin hydrolysate (FKH) results in a characteristic mix of free L-amino acids (≥ 83.5%). FKH was administered as a food supplement to a panel of adult women showing aging physiological signs. METHODS: Participants were randomly assigned in three groups to receive daily dosages of 500 or 1000 mg of FKH or placebo for 90 days. Parameters of skin roughness, wrinkle features, deep skin moisturization, skin maximum elongation and elasticity, skin thickness, skin anisotropy, skin density, gloss of skin, hair and nails, and nail hardness were evaluated. Subjects also answered a questionnaire related to the treatment efficacy perception. RESULTS: Both FKH treatments showed a significant improvement of all parameters compared to day 0 and to placebo, with an exception for fiber anisotropy and fiber density which showed a significant improvement compared to day 0 and a tendency to improve compared to placebo. These measurements were bolstered by the results of a self-assessment questionnaire, showing an overall set of positive answers for both treatments compared to placebo. CONCLUSIONS: Oral supplementation of FKH for 90 days is associated with an improvement in the appearance of facial skin, hair, and nails. This study highlights the benefits of free L-amino acids mix as potential aminobiotics and not just as building blocks of proteins, suggesting a new perspective of nutricosmetic food. © 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

The World Allergy Organization recommends probiotics in the prevention of atopic dermatitis in high-risk populations. Mutations in the filaggrin gene (FLG) result in an increased risk of atopic dermatitis through disruption of the skin keratin layer. This exploratory study investigated whether the preventive effect of maternal probiotics was evident in children with and without FLG mutations. DNA was collected from children (n = 228) from the Probiotic in the Prevention of Allergy among Children in Trondheim (ProPACT) study. Samples were analysed for 3 common FLG mutations (R501X, R2447X, and 2282del4). Overall, 7% of children had heterozygous FLG mutations; each child had only one of the 3 mutations. Mutation status had no association with atopic dermatitis (RR = 1.1; 95% CI 0.5 to 2.3). The risk ratio (RR) for having atopic dermatitis following maternal probiotics was 0.6 (95% CI 0.4 to 0.9) and RR was similar if the child expressed an FLG mutation (RR = 0.6; 95% CI 0.1 to 4.1) or wildtype FLG (RR = 0.6; 95% CI 0.4 to 0.9). The preventive effect of probiotics for atopic dermatitis was also evident in children without FLG mutation. Larger confirmatory studies are needed.

Drug-induced liver injury (DILI) is a challenge in clinical medicine and drug development. Highly sensitive novel biomarkers have been identified for detecting DILI following a paracetamol overdose. The study objective was to evaluate biomarker performance in a 14-day trial of therapeutic dose paracetamol. The PATH-BP trial was a double-blind, placebo-controlled, crossover study. Individuals (n = 110) were randomized to receive 1 g paracetamol 4× daily or matched placebo for 2 weeks followed by a 2-week washout before crossing over to the alternate treatment. Blood was collected on days 0 (baseline), 4, 7, and 14 in both arms. Alanine transaminase (ALT) activity was measured in all patients. MicroRNA-122 (miR-122), cytokeratin-18 (K18), and glutamate dehydrogenase (GLDH) were measured in patients who had an elevated ALT on paracetamol treatment (≥50% from baseline). ALT increased in 49 individuals (45%). All 3 biomarkers were increased at the time of peak ALT (K18 paracetamol arm: 18.9 ± 9.7 ng/ml, placebo arm: 11.1 ± 5.4 ng/ml, ROC-AUC = 0.80, 95% CI 0.71-0.89; miR-122: 15.1 ± 12.9fM V 4.9 ± 4.7fM, ROC-AUC = 0.83, 0.75-0.91; and GLDH: 24.6 ± 31.1U/l V 12.0 ± 11.8U/l, ROC-AUC = 0.66, 0.49-0.83). All biomarkers were correlated with ALT (K18 r = 0.68, miR-122 r = 0.67, GLDH r = 0.60). To assess sensitivity, biomarker performance was analyzed on the visit preceding peak ALT (mean 3 days earlier). K18 identified the subsequent ALT increase (K18 ROC-AUC = 0.70, 0.59-0.80; miR-122 ROC-AUC = 0.60, 0.49-0.72, ALT ROC-AUC = 0.59, 0.48-0.70; GLDH ROC-AUC = 0.70, 0.50-0.90). Variability was lowest for ALT and K18. In conclusion, K18 was more sensitive than ALT, miR-122, or GLDH and has potential significant utility in the early identification of DILI in trials and clinical practice. © The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology.

OBJECTIVE: The aim of the work described here was to develop and validate a predictive model for cytokeratin 7 (CK7) expression in clear cell renal cell carcinoma (ccRCC) patients by combining multimodal ultrasound diagnostic techniques. METHODS: This retrospective study enrolled 157 surgically confirmed ccRCC patients. All patients underwent pre-operative multimodal ultrasound diagnostic examinations, including B-mode ultrasound (US), color Doppler flow imaging (CDFI) and contrast-enhanced ultrasound (CEUS). The patients were randomly divided into a training group (103 cases) and a testing group (54 cases). Univariate and multivariate logistic regression analyses were performed in the training group to identify independent indicators associated with CK7 positivity. These indicators were included in the predictive model. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the model's discriminative ability and accuracy. Decision curve analysis (DCA) and nomogram visualization were used to assess the clinical utility of the predictive model. RESULTS: Univariate logistic regression analysis revealed that US and CDFI observations were not correlated with CK7 expression and could not predict it. Multivariate logistic regression analysis identified age (odds ratio [OR] = 0.953, 95% confidence interval [CI]: 0.909-0.999), wash-in pattern (OR = 0.180, 95% CI: 0.063-0.513) and enhancement homogeneity (OR = 11.610, 95% CI: 1.394-96.675) as independent factors related to CK7 positivity in ccRCC. Incorporating these variables into the predictive model resulted in areas under the receiver operating characteristic curve of 0.812 (95% CI: 0.711-0.913) for the training group and 0.792 (95% CI: 0.667-0.924) for the testing group. The calibration curve and DCA revealed that the model had good accuracy and clinical utility of the model. CONCLUSION: The combination of multimodal ultrasound diagnostic techniques in constructing a predictive model for CK7 expression in ccRCC patients has significant predictive value.

Purpose: Radiotherapy (RT) is commonly used in the treatment of breast cancer and often, despite advances in fractionated dosing schedules, produces undesirable skin toxicity. The purpose of this study was to evaluate the feasibility of using a keratin-based topical cream, KeraStat® Cream (KC; KeraNetics, Inc., Winston Salem, NC, USA) to manage the symptoms of radiation dermatitis (RD) in breast cancer patients undergoing RT. Materials and Methods: A total of 24 subjects were enrolled on this single-center, randomized, open-label study. Participants were randomly assigned to KC or standard of care (SOC, patient's choice of a variety of readily available creams or moisturizers). Patients were asked to apply the assigned treatment to the irradiated area twice daily, beginning with day 1 of RT, through 30 days post-RT. The primary outcome was compliance of use. Secondary outcomes included safety and tolerability of KC, as well as RD severity assessed using the Radiation Therapy Oncology Group (RTOG) scale and the patient-reported Dermatology Life Quality Index (DLQI). Results: All subjects in the KC group were assessed as compliant with no adverse events. The rate of RTOG Grade 2 RD was lower in the KC group (30.8%) compared to the SOC group (54.5%, P = .408). At the final RT visit, the mean RTOG RD score was lower in the KC group (1.0) versus the SOC group (1.4). Similarly, patient-reported quality of life measured by the DLQI at the end of RT was improved in the KC group (mean 4.25, small effect) versus the SOC group (mean 6.18, moderate effect, P = .412). Conclusions: KC was safe and well tolerated with no adverse events. Though efficacy measures were not powered to draw definitive conclusions, trends and clinical assessments suggest that there is a benefit of using KC compared to SOC for breast cancer patients treated with RT, and a larger powered study for efficacy is warranted. Trial Registry: This clinical trial is registered as NCT03374995 titled KeraStat(R) Cream for Radiation Dermatitis.

We report on the synergic effect of surfactants and chelating agents on the mechanism to remove stubborn keratin grime (keratin-Ca), which is bound with calcium ions and one of the most difficult grimes to remove, in order to make it easier to clean bathtubs in less time and with less scrubbing. Our approach was to focus on keratin swelling, which we achieved by applying aqueous solutions with chelating agents and anionic surfactants, the combination of which greatly improved the swelling ratio, resulting in quick, easy removal of keratin-Ca with water rinsing and little scrubbing. For the swelling process, we added chelating agents and anionic surfactants to swell the keratin-Ca by both capturing calcium ions and improving solution permeation. Furthermore, we measured the structural change of the keratin-Ca during swelling by TD-NMR and confirmed that a certain combination of chelating agent and anionic surfactant improved swelling by affecting not only the amorphous part such as the keratin matrix, but also the crystalline part such as the intermediate filaments (IFs).

The combination of chemotherapy and photodynamic therapy (PDT) is considered a valuable strategy for increasing therapeutic response in cancer treatment, and the re-formulation of pharmaceuticals in biocompatible nanoparticles (NPs) is particularly appealing for the possibility of co-loading drugs exerting cytotoxicity by different mechanisms, with the aim to produce synergic effects. We report the in-water synthesis of a novel keratin-based nanoformulation for the co-delivery of the antimitotic Docetaxel (DTX) and the photosensitizer Chlorin e6 (Ce6). The drug-induced aggregation method allowed the formation of monodisperse NPs (DTX/Ce6-KNPs) with an average diameter of 133 nm and loaded with a drug ratio of 1:1.8 of Ce6 vs DTX. The efficacy of DTX/Ce6-KNPs was investigated in vitro in monolayers and spheroids of DTX-sensitive HeLa (HeLa-P) and DTX-resistant HeLa (HeLa-R) cells. In monolayers, the cytotoxic effects of DTX/Ce6-KNPs toward HeLa-P cells were comparable to those induced by free DTX + Ce6, while in HeLa-R cells the drug co-loading in KNPs produced synergic interaction between chemotherapy and PDT. Moreover, as respect to monotherapies, DTX/Ce6-KNPs induced stronger cytotoxicity to both HeLa-P and HeLa-R multicellular spheroids and reduced their volumes up to 50%. Overall, the results suggest that KNPs are very promising systems for the co-delivery of chemotherapeutics and PSs, favoring synergic interactions between PDT and chemotherapy.

BACKGROUND: The POP Trial was a phase 1, open-label, rising-dose, randomised study that explored the safety and tolerability of calmangafodipir (superoxide dismutase mimetic) co-treatment with n-acetylcysteine (NAC) for paracetamol overdose. METHODS: Patients were recruited at the Royal Infirmary of Edinburgh (8th June 2017-10th May 2018). Inclusion criterion: adults within 24 h of a paracetamol overdose that required NAC. Within each of 3 sequential cohorts, participants were randomly assigned, with concealed allocation, to NAC and a single intravenous calmangafodipir dose (n = 6) or NAC alone (n = 2). Calmangafodipir doses were 2, 5, or 10 μmol/kg. Participants, study and clinical teams were not blinded. The primary outcome was safety and tolerability. Secondary outcomes were alanine transaminase (ALT), international normalised ratio (INR), keratin-18, caspase-cleaved keratin-18 (ccK18), microRNA-122, and glutamate dehydrogenase (GLDH). (Clinicaltrials.gov:NCT03177395). FINDINGS: All 24 participants received their allocated drug doses and were analysed. Primary endpoints: all participants experienced ≥1 adverse event (AE), most commonly gastrointestinal. Patients experiencing ≥1 serious adverse event (SAE): NAC alone, 2/6; NAC + calmangafodipir (2 μmol/kg), 4/6; NAC + calmangafodipir (5 μmol/kg), 2/6; NAC + calmangafodipir (10 μmol/kg), 3/6. No AEs or SAEs were probably or definitely calmangafodipir-related. Secondary safety outcomes demonstrated no differences between groups. With NAC alone, 2/6 had ALT > 100 U/L; with NAC + calmangafodipir, 0/18. No INR difference. Keratin-18 and ccK18 increased in the NAC alone group more than with calmangafodipir (baseline to 20 h fold change, NAC + calmangafodipir (5 μmol/kg) compared to NAC alone: 0.48 (95%CI 0.28-0.83)). microRNA-122 changes were similar to K18, GLDH was frequently undetected. INTERPRETATION: Calmangafodipir was tolerated when combined with NAC and may reduce biomarkers of paracetamol toxicity.

Chinese tree shrew, an animal exhibited closer evolutionary relationship with humans compared to rodents, is getting increasingly attentions as an appealing experimental animal model for human diseases. However, a high-efficiency and stable method to establish tree shrew breast precancerous lesions model has not been clearly elucidated. Thus, the current study aimed to explore the way of establishing breast precancerous model in tree shrew and investigate the pathologic characteristics of induced breast precancerous lesions. The results indicated that 7,12-dimethylbenz(a)anthracene (DMBA) could induce breast lesions in tree shrews. However, comparing to DMBA alone, an addition of medroxyprogesterone acetate (MPA) to DMBA critically increased the rate of induced breast lesion in tree shrews. Half of induced breast lesions were intraductal papilloma and the others were atypical ductal hyperplasia. Induced lesions showed positive expression of estrogen receptor α (ERα), progesterone receptor (PR) and cytokeratin 5/6 (CK5/6), but negative expression of human epidermal growth factor receptor-2 (Her-2). The expression of B cell lymphoma-extra large (Bcl-xl) was significantly higher and the expression of B cell lymphoma 2 associated X protein (Bax) was significantly lower in the precancerous lesions (atypical ductal hyperplasia) compared to benign tumor (intraductal papilloma). These results suggest that DMBA is able to induce breast lesions in tree shrews. Combination of DMBA and MPA may be more effective to establish breast precancerous lesion tree shrew models. Tree shrew might be a promising animal model for studying the tumorogenesis of breast cancer.

BACKGROUND Calcipotriol ointment has been demonstrated to be a very safe and effective topical drug for psoriasis. This study aims to investigate the effect of calcipotriol on IFN-γ-induced keratin 17 (K17) expression in a human keratinocyte cell line (HaCaT), which is a widely accepted as a mimic in vitro model for psoriasis. MATERIAL AND METHODS We used Western blot, immunofluorescence staining, and luciferase reporter system assays to evaluate the expression of K17 and the possible underlying mechanisms. RESULTS Administration of IFN-γ (125-1000 U) increased K17 expression in a dose-dependent manner, and 250 U/ml IFN-γ significantly elevated K17 expression. The experimental results showed that calcipotriol at concentrations of 10^-7 M and 10^-5 M suppressed the IFN-γ-induced K17 expression by 58.10% and 70.68%, respectively. Through immunofluorescence staining and luciferase reporter assay, we found that Vitamin D Response Element (VDRE) affected IFN-activated site (Gamma-activated sequence, GAS) function at the transcriptional level and was involved in the inhibition of K17 expression. CONCLUSIONS Our data suggest that calcipotriol downregulates IFN-γ-mediated K17 expression in keratinocytes in a dose-dependent manner via VDRE effect GAS function. The inhibitory effect of calcipotriol on K17 expression may be a potential mechanism and function in the treatment psoriasis.

BACKGROUND: Endometriosis is one of the most common chronic gynecological diseases. OBJECTIVES: The aim of the study was to examine the effects of curcumin and/or deferoxamine on cell proliferation in a rat model of endometriosis. MATERIAL AND METHODS: Thirty female 12-week-old albino Wistar rats, weighing 200-250 g, were used in this study. All the rats underwent ovariectomy and 0.1-mg β-estradiol 17-valerate pellets were placed intraperitoneally. An experimental model of endometriosis was created in all the animals. To create the experimental model, an approximately 1-cm long section of the uterus was taken, primarily from the right horn of the uterus. Autologous fragments were then placed between the peritoneum and muscle. The animals were divided into 3 groups: Group A, treated only with the vehicle used for curcumin and deferoxamine; group B, treated with curcumin (100 mg/kg body weight); and group C, treated with deferoxamine + curcumin (100 mg/kg body weight). After biopsy samples were obtained, the sections were stained with hematoxylin and eosin. Immunostaining for cytokeratin-7 and proliferating cell nuclear antigen (PCNA) was performed. Blood iron levels were measured using a Perkin Elmer AAnalyst 800 Atomic Absorption Spectrophotometer. RESULTS: The endometrial implant size increased in Group A, but treatment with curcumin (p = 0.01) and deferoxamine + curcumin (p = 0.007) reduced the implant size. In ectopic endometrial epithelial cells, there were significant decreases in PCNA immunoreactivity between groups A and B (p = 0.044) and between groups A and C (p = 0.033). CONCLUSIONS: Treatment with curcumin alone and/or in combination with deferoxamine contributed to a reduction in implant size and cell proliferation in a rat endometriosis model. Iron-chelating agents may act in the same manner when used in women with endometriosis; however, further studies from different perspectives are still needed.

We hypothesised that Hansen Solubility Parameters (HSPs) can be used to predict drug-nail affinities. Our aims were to: (i) determine the HSPs (δD, δP, δH) of the nail plate, the hoof membrane (a model for the nail plate), and of the drugs terbinafine HCl, amorolfine HCl, ciclopirox olamine and efinaconazole, by measuring their swelling/solubility in organic liquids, (ii) predict nail-drug interactions by comparing drug and nail HSPs, and (iii) evaluate the accuracy of these predictions using literature reports of experimentally-determined affinities of these drugs for keratin, the main constituent of the nail plate and hoof. Many solvents caused no change in the mass of nail plates, a few solvents deswelled the nail, while others swelled the nail to varying extents. Fingernail and toenail HSPs were almost the same, while hoof HSPs were similar, except for a slightly lower δP. High nail-terbinafine HCl, nail-amorolfine HCl and nail-ciclopirox olamine affinities, and low nail-efinaconazole affinities were then predicted, and found to accurately match experimental reports of these drugs' affinities to keratin. We therefore propose that drug and nail Hansen Solubility Parameters may be used to predict drug-nail interactions, and that these results can assist in the design of drugs for the treatment of nail diseases, such as onychomycosis and psoriasis. To our knowledge, this is the first report of the application of HSPs in ungual research.

Hepatocellular carcinoma (HCC) is highly resistant to conventional systemic therapies and prognosis for advanced HCC patients remains poor. Recent studies of the molecular mechanisms responsible for tumor initiation and progression have identified several potential molecular targets in HCC. Sorafenib is a multi-kinase inhibitor shown to have survival benefits in advanced HCC. It acts by inhibiting the serine/threonine kinases and the receptor type tyrosine kinases. In preclinical experiments sorafenib had anti-proliferative activity in hepatoma cells and it reduced tumor angiogenesis and increased apoptosis. Here, we demonstrate for the first time that the cytotoxic mechanisms of sorafenib include its inhibitory effects on protein ubiquitination, unfolded protein response (UPR) and keratin phosphorylation in response to endoplasmic reticulum (ER) stress. Moreover, we show that combined treatment with sorafenib and proteasome inhibitors (PIs) synergistically induced a marked increase in cell death in hepatoma- and hepatocyte-derived cells. These observations may open the way to potentially interesting treatment combinations that may augment the effect of sorafenib, possibly including drugs that promote ER stress. Because sorafenib blocked the cellular defense mechanisms against hepatotoxic injury not only in hepatoma cells but also in hepatocyte-derived cells, we must be careful to avoid severe liver injury.

The stem cell niche is crucial to the control of stem cell fate determination in vitro as well as in vivo, and an understanding of these niches is required for the progression of stem cell and tissue engineering. The goal of our study was to commit human mesenchymal stem cells (hMSCs) to the epithelial lineage. To do this, we cultured bone marrow-derived mesenchymal stem cells (MSCs) on plates coated with type I collagen gel with or without 10 μM all-trans retinoic acid (ATRA).We found depth-dependent differentiation of hMSCs to the epithelial lineage, with the thick collagen gel (1900 μm) generating more than 80% cytokeratin-18 (CK-18)-positive cells, whereas the thin collagen gel (100 μm) generated significantly fewer CK-18-positive cells. In addition, we found that supplementation of 10 μM ATRA enhanced CK-18 expression and induced cluster-formation in cells grown on the thick collagen gel. The effect of gel depth on hMSC differentiation appears to be caused by partial cytoskeletal disruption.These results suggest that ATRA and a collagen extracellular matrix may have a synergistic effect on differentiation of human mesenchymal stem cells to epithelial lineage.

Immunofluorescent serum studies of the roles of the two groups of normal complement-fixing autoantibodies in psoriasis are complicated by the interference phenomenon. Both antibodies have the potential to react in vivo at sites of trauma and in psoriasiform lesions. In serum tests, only one or the other reacts, as demonstrated by immunofluorescent serum tests and absorption studies with isolated stratum corneum antigen. In tests of 15 normal sera, only one consistently reacted with the soluble carbohydrate antigens; the rest consistently reacted with the glycoproteins of the keratin intermediate filaments. This appears to be due to an antibody interference reaction that permits only one of two or more antibodies to react on a given tissue section.

Keratinocytes can be activated by Cutibacterium acnes, leading to the production of proinflammatory cytokines via toll-like receptors (TLRs) 2 and 4. Although several studies have investigated keratinocytes, the mechanism of calcium-mediated activation remains unclear. Herein, we investigated whether calcium influx via TLR2 and TLR4 stimulation was involved in cytokine secretion by keratinocytes in HaCaT cells. Although TLR2 stimulation by peptidoglycan (PGN) increased intracellular calcium influx, TLR4 stimulation by lipopolysaccharide (LPS) did not increase it, as analyzed using flow cytometry with the calcium indicator Fluo-3. However, activation by either TLR2 or TLR4 ligands upregulated the intracellular calcium influx in THP-1 monocytes. Additionally, the expression of major proinflammatory cytokines and chemokines, such as interleukin (IL)-6, IL-8, IL-1α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein-1 (MCP-1), was significantly increased by TLR2 in HaCaT cells. Moreover, treatment with the intracellular calcium chelator, BAPTA-AM, disrupted PGN-mediated induction of IL-6, IL-8, and MCP-1 production. Real-time quantitative polymerase chain reaction (PCR) and western blotting revealed that TLR2 stimulation induced expression of the epidermal differentiation marker keratin 1. In conclusion, TLR2-induced intracellular calcium influx plays a pivotal role in the secretion of proinflammatory cytokines, such as IL-6 and MCP-1, in keratinocytes. Moreover, the continuous influx of calcium via TLR2 activation leads to keratinization. In vitro studies using HaCaT cells provide basic research on the effect of TLR2-induced calcium on C. acnes-mediated inflammation in keratinocytes. These studies are limited in their ability to clinically predict what happens in human keratinocytes. Clinical studies on patients with acne, including three-dimensional (3D) cultures of primary keratinocytes, are required to develop new diagnostic markers for determining the severity of acne vulgaris.

Although hepatocellular carcinoma (HCC) is developed with various etiologies, protection of hepatocytes seems basically essential to prevent the incidence of HCC. Keratin 8 and keratin 18 (K8/K18) are cytoskeletal intermediate filament proteins that are expressed in hepatocytes. They maintain the cell shape and protect cells under stress conditions. Their protective roles in liver damage have been described in studies of mouse models, and K8/K18 mutation frequency in liver patients. Interestingly, K8/K18 bind to signaling proteins such as transcription factors and protein kinases involved in HCC development. Since K8/K18 are abundant cytoskeletal proteins, K8/K18 binding with the signaling factors can alter the availability of the factors. Herein, we discuss the potential roles of K8/K18 in HCC development.

Lip squamous cell carcinoma (SCC) accounts for approximately 30% of oral malignancies. Delayed diagnosis worsens the prognosis, leading to tumor growth, regional lymph node involvement, distant metastasis, and the need for invasive therapy. Dermoscopy is a practical, low-cost, and non-invasive diagnostic tool used to detect skin tumors. This review analyzed the common dermoscopic features of lip SCC and actinic cheilitis (AC). A search of MEDLINE, EMBASE, and Web of Science was made for original dermatoscopy studies. Pooled proportions were calculated using a random-effects model (95% CI). Eleven studies were included: 325 patients, 205 lip SCCs, and 122 ACs. Key dermoscopic findings in lip SCCs were white structureless areas 61.9%, ulceration 59.3%, white halos 57.7%, keratin scales 54.98%, pinkish-red background 50.5%, whitish-yellow colors 41.8%, and shiny white streaks 24.5%. Polymorphous vessels were found in 55.8%, and monomorphous in 44.1%. Vessel morphology was hairpin 30.90%, serpentine 22.27%, dotted 21.46%, and glomerular 11.20%. ACs exhibited white halos in 66.14% of cases, white structureless areas in 59.62%, white scales in 57.90%, yellow scales in 30.14%, ulceration in 32.43%, white circles in 9.94%, and had polymorphous (72.93%), hairpin (30.83%), or dotted (20.71%) vessels. Dermoscopy aids early detection of lip SCC and AC, though overlapping features can limit accurate distinction. Histopathological confirmation remains essential in difficult cases, and further studies should explore subgroup-specific dermoscopic patterns. © 2025 Deutsche Dermatologische Gesellschaft (DDG).

BACKGROUND: To systematically review the literature on clinicopathological features of keratoacanthomas (KA) in the oral and perioral region. MATERIAL AND METHODS: The review protocol as registered under the number CRD42022323274. Electronic searches were conducted in four databases with a specific search strategy using MeSH and free terms. RESULTS: 60 studies reporting 73 cases of KA were included in this systematic review. KA affects more men with a mean age of 49.09 years old. Sun-exposed area of the lower lip was the most common anatomical location of the perioral lesions (38.35%) and the oral mucosa (9.58%) of the intra-oral ones. The most frequent clinical presentation of the perioral lesions was of an ulcerated nodule (36.23) and intra-orally of an papule (11.59) or nodule (11.59). Incisional biopsies were the commonest procedure for the diagnosis. The histological findings commonly presented a hyperplastic epithelial tissue forming a crater-like structure filled with keratin. Slightly atypia, keratin pearls and an inflammatory infiltrate in connective tissue could also be seen. Surgical excision was the treatment of choice in the majority of cases (45.71%). A low recurrence rate (6.89%) was seen in a mean follow-up time of 20.54 months. CONCLUSIONS: KA affects commonly sun-exposed areas of men in their sixth decade of life. Given the similarity of squamous cell carcinoma, it is important to study KA to help clinicians with the correct diagnosis and treatment.

OBJECTIVE: Early diagnosis of oral squamous cell carcinoma (OSCC) is a global concern, particularly in low-resource environments where invasive diagnostics limit population-wide screening. The purpose of this review is to evaluate the potential of salivary biomarkers: Interleukin-8 (IL-8), Cytokeratin 19 fragment (CYFRA 21-1), and Cluster of Differentiation 44 (CD44) in OSCC diagnosis. METHODS: A methodical search was conducted across PubMed, Embase, Scopus, and Web of Science databases till December 2024. Following PRISMA guidlines, studies quantifying salivary IL-8, CYFRA 21-1, and CD44 levels in OSCC patients and healthy controls were included. Using a bivariate random-effects model, we retrieved and combined sensitivity, specificity, and area under the summary receiver operating characteristic (SROC) curve. The QUADAS-2 tool was used to evaluate risk of bias. A standardized mean difference (SMD) meta-analysis was also performed to assess quantitative elevation in biomarker levels between cases and controls. RESULTS: Out of 311 articles reviewed, 20 eligible studies were included. IL-8, CYFRA 21-1, and CD44, individually, each biomarker demonstrated good diagnostic accuracy (with pooled AUCs of 0.88, 0.90, and 0.91, respectively), with CD44 showing overall highest diagnostic consistency. The combined biomarker panel exhibited significantly enhanced diagnostic precision (pooled AUC: 0.92; sensitivity: 88 %; specificity: 90 %). This combined metric was derived using a bivariate meta-analysis model applied to studies that evaluated at least two or more of the three biomarkers together. These findings were supported by corresponding forest plots and SROC curves, demonstrating low publication bias and moderate heterogeneity. Consistency across sample size, geographic origin, and assay technique were verified by subgroup analyses. CONCLUSION: Salivary IL-8, CYFRA 21-1, and CD44 taken together provide a scientifically strong, non-invasive method for OSCC diagnosis on a uniform diagnostic panel. With good translational potential in both clinical and community-based screening systems. These results provide a strong scientific foundation for the development of a saliva

INTRODUCTION: Clinical research on innovative therapies for the rare genodermatosis epidermolysis bullosa (EB) faces significant challenges, including small sample sizes, disease heterogeneity with intra- and inter-individual variability, limited understanding of pathogenic mechanisms and natural disease course, as well as the lack of patient-centred core outcomes. Moreover, existing tools and techniques to assess disease activity and dynamics are heterogeneous, inconsistent, and may fail to consider or inaccurately emphasize particularities of individual patients and distinct EB subtypes. METHODS: In order to exemplify the differences between keratin-associated subtypes of EB simplex (k-EBS), we summarized respective clinical characteristics in a narrative way. In addition, we performed a systematic review of the literature published over the last 5 years, with the aim to give an overview on outcomes and their assessments used in these patient populations. RESULTS: This review summarises the methodological scope, strengths and limitations of outcome assessments in clinical trials for the k-EBS, a group of inherited skin fragility diseases characterised by their distinct phenotype of epidermal blistering. CONCLUSIONS: By presenting an overview of the clinical spectrum of k-EBS, we identified key gaps in current assessment methodologies and propose alternative approaches to optimise the evaluation of skin blistering, with the aim of enhancing the accuracy, reliability, and patient-relevance of clinical outcomes. © 2025. The Author(s).

Monilethrix is a rare congenital hair disorder characterized by fragile, beaded hair shafts due to mutations in various keratin or desmoglein 4 genes. A systematic review of 24 studies (16 pediatric only, 3 mixed adult and pediatric, 3 adult only, and 2 unspecified) evaluating various treatment modalities identified topical and oral minoxidil as the most effective therapies, while oral retinoids and other treatments showed variable efficacy. Further pediatric research and clinical studies are necessary to assess long-term treatment outcomes and explore novel therapeutic strategies for this challenging condition. © 2025 The Author(s). Pediatric Dermatology published by Wiley Periodicals LLC.

BACKGROUND: This meta-analysis aimed to summarize the diagnostic accuracy and cut-off values of cytokeratin (CK) 18 measurements, specifically M30 and M65, as candidate biomarkers for the pathological evaluation of biopsy specimens used to stage liver inflammation and fibrosis in patients with chronic liver diseases. METHODS: Databases were searched for studies collected up to January 11th, 2025. Pooled sensitivity, specificity, area under the receiver-operating characteristic curves, and mean cut-off values were calculated using random-effects models regardless of heterogeneity. A meta-regression analysis and subgroup analysis were performed to explore heterogeneity. RESULTS: Sixty-three studies comprising 9137 patients were included. The summarized AUROC curve of CK18 M30 for the diagnosis of significant liver inflammation, fibrosis ≥F1, ≥F2, ≥F3, and =F4 according to the METAVIR score system were 0.82, 0.75, 0.78, 0.78 and 0.76, with mean cut-off values of 264.3, 188.0, 276.9, 322.8 and 169.4 U/L. For M65, the summarized AUROC curve for detecting significant liver inflammation, fibrosis ≥F1, ≥F2, and =F4 were 0.79, 0.70, 0.76, 0.64 and 0.72, with mean cut-off values of 541.1, 417.6, 500.1, 424.6 and 674.0 U/L. The subgroup analyses implied that ethnicity may be the primary factor related to heterogeneity in CK18 M30 when applied to detect significant inflammation. Asian patients had values 79.7 U/L higher than those of non-Asian patients (p = 0.0157). CONCLUSIONS: CK18 M30 and M65 have clinically meaningful accuracy as alternative diagnostic tools for determining liver inflammation and fibrosis using biopsy specimens of patients with steatotic liver disease or viral hepatitis. REGISTRATION: PROSPERO registration number: CRD42022364598.

BACKGROUND: Cytokeratins are intracellular proteins known as diagnostic biomarkers or prognostic factors for certain cancers. Cytokeratin 19 (CK-19) expression has been proven to have prognostic value for some cancers, but its relationship with others, such as prostate cancer (PCa), remains unclear. This systematic review article aimed to examine the relationship between CK-19 expression and prostate adenocarcinoma (PAC). METHODS: To include the eligible studies that detected CK-19 expression in PAC, published articles since June 2024 were found using PubMed, Scopus, and Web of Science databases. The "prostate cancer" and "cytokeratin 19" keywords and their Mesh term were used for search databases. Data from the included articles were extracted and tabulated. This study was performed using the PRISMA guidelines, and the JBI checklist was used for the quality assessment. The study protocol was registered in PROSPERO under the "CRD42023472637" code. RESULTS: Twenty-one studies were included. Eleven studies used reverse transcription polymerase chain reaction (RT-PCR) to investigate CK-19 expression, four used immunohistochemistry (IHC) staining, three used both one-step nucleic acid amplification (OSNA) and hematoxylin and eosin (H&E) methods, and three used the electrochemiluminescence (ECL) technique. CK-19 expression was detected in 301 patients among 619 patients. Additionally, only five out of 80 healthy donors were positive for CK-19 expression. CONCLUSION: Available evidence indicates a correlation between CK-19 expression and PAC progression, with higher CK-19 levels associated with advanced stages and worse prognosis. The overall evidence suggests that CK-19 could serve as a diagnostic and prognostic marker in PAC. © 2025. The Author(s).