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The cytoskeleton of the cell is constantly exposed to physical forces that regulate cellular functions. Selected members of the LIM (Lin-11, Isl-1, and Mec-3) domain-containing protein family accumulate along force-bearing actin fibers, with evidence supporting that the LIM domain is solely responsible for this force-induced interaction. However, LIM domain's force-induced interactions are not limited to actin. LIMK1 and LMO1, both containing only two tandem LIM domains, are recruited to force-bearing keratin fibers in epithelial cells. This unique recruitment is mediated by their LIM domains and regulated by the sequences outside the LIM domains. Based on in vitro reconstitution of this interaction, LIMK1 and LMO1 directly interact with stretched keratin 8/18 fibers. These results show that LIM domain's mechano-sensing abilities extend to the keratin cytoskeleton, highlighting the diverse role of LIM proteins in force-regulated signaling.

ABSTRACT Raman spectra of human hair cuticle measured in two experimental configurations with linearly polarized radiation focused on the lateral surface of the hair and on its cross section are compared. The bands at ~150, 220–230, 900, 935, 1321, 1338, and 1652 cm−1 are found to be polarization‐sensitive and assigned to the skeletal vibrations of α‐helices of hair keratins. However, different Raman spectra depending on the relative direction of signal collection can be obtained under identical polarization conditions for excitation. Several markers of the secondary structure of keratins (in particular, ~150, 935, and 1338 cm−1) may also be sensitive to the changes in the tertiary structure. [ABSTRACT FROM AUTHOR]

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Rhabdomyosarcoma (RMS) comprises of heterogeneous group of neoplasms that occasionally express epithelial markers on immunohistochemistry (IHC). We herein report the case of a patient who developed RMS of the skull with EWSR1 fusion and anaplastic lymphoma kinase (ALK) and cytokeratin expression as cytomorphologic features. A 40-year-old man presented with a mass in his forehead. Surgical resection was performed, during which intraoperative frozen specimens were obtained. Squash cytology showed scattered or clustered spindle and epithelioid cells. IHC revealed that the resected tumor cells were positive for desmin, MyoD1, cytokeratin AE1/AE3, and ALK. Although EWSR1 rearrangement was identified on fluorescence in situ hybridization, ALK, and TFCP2 rearrangement were not noted. Despite providing adjuvant chemoradiation therapy, the patient died of tumor progression 10 months after diagnosis. We emphasize that a subset of RMS can express cytokeratin and show characteristic histomorphology, implying the need for specific molecular examination.

Objectives To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC). Methods We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses. Results Patients with advanced-stage, low K17 PDACs treated using 5-fluorouracil (5-FU)–based chemotherapeutic regimens had 3-fold longer survival than corresponding cases treated with gemcitabine-based chemotherapy. By contrast, PDACs with high K17 did not respond to either regimen. The predictive value of K17 was independent of tumor mutation status and other clinicopathologic variables. Conclusions The detection of K17 in 10% or greater of PDAC cells identified patients with shortest survival. Among patients with low K17 PDACs, 5-FU–based treatment was more likely than gemcitabine-based therapies to extend survival. [ABSTRACT FROM AUTHOR]

Keratin intermediate filaments form dynamic filamentous networks, which provide mechanical stability, scaffolding, and protection against stress to epithelial cells. Keratins and other intermediate filaments have been increasingly linked to the regulation of mitochondrial function and homeostasis in different tissues and cell types. While deletion of keratin 8 (K8–/–) in mouse colon elicits a colitis-like phenotype, epithelial hyperproliferation, and blunted mitochondrial ketogenesis, the role of K8 in colonocyte mitochondrial function and energy metabolism is unknown. We used two K8 knockout mouse models and CRISPR/Cas9 K8–/– colorectal adenocarcinoma Caco-2 cells to answer this question. The results show that K8–/– colonocyte mitochondria in vivo are smaller and rounder and that mitochondrial motility is increased in K8–/– Caco-2 cells. Furthermore, K8−/− Caco-2 cells displayed diminished mitochondrial respiration and decreased mitochondrial membrane potential compared with controls, whereas glycolysis was not affected. The levels of mitochondrial respiratory chain complex proteins and mitochondrial regulatory proteins mitofusin-2 and prohibitin were decreased both in vitro in K8–/– Caco-2 cells and in vivo in K8–/– mouse colonocytes, and reexpression of K8 into K8–/– Caco-2 cells normalizes the mitofusin-2 levels. Mitochondrial Ca2+ is an important regulator of mitochondrial energy metabolism and homeostasis, and Caco-2 cells lacking K8 displayed decreased levels and altered dynamics of mitochondrial matrix and cytoplasmic Ca2+. In summary, these novel findings attribute an important role for colonocyte K8 in stabilizing mitochondrial shape and movement and maintaining mitochondrial respiration and Ca2+ signaling. Further, how these metabolically compromised colonocytes are capable of hyperproliferating presents an intriguing question for future studies. NEW & NOTEWORTHY: In this study, we show that colonocyte intermediate filament protein keratin 8 is important for stabilizing mitochondria and maintaining mitochondrial energy metabolism, as keratin 8-deficient colonocytes display smaller, rounder, and more motile mitochondria, diminished mitochondrial respiration, and altered Ca2+ dynamics. Changes in fusion-regulating proteins are rescued with reexpression of keratin 8. These alterations in colonocyte mitochondrial homeostasis contribute to keratin 8-associated colitis pathophysiology. [ABSTRACT FROM AUTHOR]

Keratins 6, 16, and 17 occupy unique positions within the keratin family. These proteins are not commonly found in the healthy, intact epidermis, but their expression increases in response to damage, inflammation, and hereditary skin conditions, as well as cancerous cell transformations and tumor growth. As a result, there is an active investigation into the potential use of these proteins as biomarkers for different pathologies. Recent studies have revealed the role of these keratins in regulating keratinocyte migration, proliferation, and growth, and more recently, their nuclear functions, including their role in maintaining nuclear structure and responding to DNA damage, have also been identified. This review aims to summarize the latest research on keratins 6, 16, and 17, their regulation in the epidermis, and their potential use as biomarkers in various skin conditions.

Although not completely understood, the role of the Hedgehog-GLI (HH-GLI) signaling pathway in melanoma and epithelial skin tumors has been reported before. In this study, we confirmed in various melanoma cell line models that keratin 16 (KRT16) and S100 Calcium-Binding Protein A7 (S100A7) are transcriptional targets of GLI Family Zinc Finger (GLI) proteins. Besides their important role in protecting and maintaining the epidermal barrier, keratins are somehow tightly connected with the S100 family of proteins. We found that stronger expression of KRT16 indeed corresponds to stronger expression of S100A7 in our clinical melanoma samples. We also report a trend regarding staining of GLI1, which corresponds to stronger staining of GLI3, KRT16, and S100A7 proteins. The most interesting of our findings is that all the proteins are detected specifically in the epidermis overlying the tumor, but rarely in the tumor itself. The examined proteins were also not detected in the healthy epidermis at the edges of the sample, suggesting that the staining is specific to the epidermis overlaying the tumor mass. Of all proteins, only S100A7 demonstrated a statistically significant trend regarding tumor staging and staining intensity. Results from our clinical samples prove that immune infiltration is an important feature of melanoma. Pigmentophages and tumor-infiltrating lymphocytes (TIL) demonstrate a significant association with tumor stage, while mononuclear cells are equally present in all stages. For S100A7, we found an association between the number of TILs and staining intensity. Considering these new findings presented in our study, we suggest a more detailed examination of the possible role of the S100A7 protein as a biomarker in melanoma. [ABSTRACT FROM AUTHOR]

Pinin (PNN) is a desmosome-associated protein that reinforces the organization of keratin intermediate filaments and stabilizes the anchoring of the cytoskeleton network to the lateral surface of the plasma membrane. The aberrant expression of PNN affects the strength of cell adhesion as well as modifies the intracellular signal transduction pathways leading to the onset of CRC. In our previous studies, we characterized the role of miR-195-5p in the regulation of desmosome junctions and in CRC progression. Here, with the aim of investigating additional mechanisms related to the desmosome complex, we identified PNN as a miR-195-5p putative target. Using a public data repository, we found that PNN was a negative prognostic factor and was overexpressed in colon cancer tissues from stage 1 of the disease. Then, we assessed PNN expression in CRC tissue specimens, confirming the overexpression of PNN in tumor sections. The increase in intracellular levels of miR-195-5p revealed a significant decrease in PNN at the mRNA and protein levels. As a consequence of PNN regulation by miR-195-5p, the expression of KRT8 and KRT19, closely connected to PNN, was affected. Finally, we investigated the in vivo effect of miR-195-5p on PNN expression in the colon of AOM/DSS-treated mice. In conclusion, we have revealed a new mechanism driven by miR-195-5p in the regulation of desmosome components, suggesting a potential pharmacological target for CRC therapy. [ABSTRACT FROM AUTHOR]

The changes in endometrial cells, both in the eutopic endometrium of patients with and without endometriosis and in lesions at ectopic sites, are frequently described and often compared to tumorigenesis. In tumorigenesis, the concept of "seed and soil" is well established. The seed refers to tumor cells with metastatic potential, and the soil is any organ or tissue that provides a suitable environment for the seed to grow. In this systematic review (PRISMA-S), we specifically compared the development of endometriosis with the "seed and soil" hypothesis. To determine changes in the endometrial seed, we re-analyzed the mRNA expression data of the eutopic and ectopic endometrium, paying special attention to the epithelial–mesenchymal transition (EMT). We found that the similarity between eutopic endometrium without and with endometriosis is extremely high (~99.1%). In contrast, the eutopic endometrium of patients with endometriosis has a similarity of only 95.3% with the ectopic endometrium. An analysis of EMT-associated genes revealed only minor differences in the mRNA expression levels of claudin family members without the loss of other cell–cell junctions that are critical for the epithelial phenotype. The array data suggest that the changes in the eutopic endometrium (=seed) are quite subtle at the beginning of the disease and that most of the differences occur after implantation into ectopic locations (=soil). [ABSTRACT FROM AUTHOR]

Mallory-Denk bodies (MDBs) are hepatocellular cytoplasmic inclusions, which occur in certain chronic liver diseases, such as alcohol-related (ASH) and metabolic dysfunction-associated (MASH) steatohepatitis, copper toxicosis, some drug-induced liver disorders, chronic cholangiopathies, and liver tumors. Our study focused on the expression of the senescence markers p21WAF1/cip1 and p16INK4a in hepatocytes containing MDBs in steatohepatitis, chronic cholangiopathies with fibrosis or cirrhosis, Wilson's disease, and hepatocellular carcinomas. Cytoplasm and nuclei of MDB-containing hepatocytes as well as MDB inclusions, except those associated with carcinoma cells, were strongly p16-positive, p21-positive, as well as p21-negative nuclei in MDB-containing hepatocytes which were observed whereas MDBs were p21-negative. Expression of the senescence marker p16 suggests that MDB formation reflects an adaptive response to chronic stress resembling senescence with its consequences, i.e., expression of inflammation- and fibrosis-prone secretome. Thus, senescence can be regarded as "double-edged sword" since, on the one hand, it may be an attempt of cellular defense, but, on the other, also causes further and sustained damage by inducing inflammation and fibrosis related to the senescence-associated secretory phenotype and thus progression of chronic liver disease. [ABSTRACT FROM AUTHOR]

Objectives Microvascular invasion (MVI) has previously been reported to be related to cancer prognosis; however, its significance in patients with dual-phenotype hepatocellular carcinoma (DPHCC) remains uncharacterized. We studied the role of MVI in the survival of patients diagnosed with DPHCC in Fujian, China, which has a high incidence of HCC. Methods Patients with DPHCC (n = 84) who had undergone surgical interventions at the 900th Hospital of the Joint Logistic Support Force between 2013 and 2019 were retrospectively analyzed using the log-rank test and Kaplan-Meier method. Univariate and multivariate Cox model analyses were also conducted to further understand the correlation between MVI and patient survival. Results Our results indicated that MVI was related to poor survival. According to the univariate analysis, MVI, the number of tumor lesions, necrosis, differentiation, peripheral hepatic fibrosis, the expression of cytokeratin 19 (CK19), and serum levels of both ɑ-fetoprotein (AFP) and cancer antigen-199 showed a strong correlation with overall survival. Necrosis and serum AFP levels were strongly related to an increased risk of death, according to the multivariate analysis. Tumor size; the number of tumor lesions; differentiation; peripheral hepatic fibrosis; liver capsule invasion; and expression of CK19, vascular endothelial growth factor, CK7, and mucin 1 showed a correlation with MVI, per the outcomes of χ2 tests. Conclusions Microvascular invasion may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival. [ABSTRACT FROM AUTHOR]

Damage caused by chemical, physical, and thermal procedures can disrupt the natural morphological characteristics of the hair, causing the strands to become dry, dull, weak, and brittle. The objective of this article was to update dermatologists on the methods available for assessing hair shaft damage. The main laboratory (microscopy, tensile strength, structural assessment, physical and mechanical properties) and outpatient (diagnostic tests and patient history) diagnostic methods for evaluating the quality of the hair shaft are presented.

Ameloblastic carcinoma is a malignant odontogenic neoplasm that has been reported only rarely in veterinary species. A 16-y-old Arabian crossbred mare was presented for evaluation of a hard mass on the body of the mandible, with evidence of osteolysis on radiographs. Incisional biopsies revealed an invasive neoplasm comprised of spindloid epithelial cells with a high mitotic count and partial dual cytokeratin-vimentin immunoreactivity. The horse was euthanized because of rapid tumor progression 3 mo after presentation. Postmortem evaluation revealed partial obliteration of the mandible by a large, firm-to-hard, tan, locally destructive and invasive mass with no gross or histologic evidence of metastasis. Postmortem histology revealed a poorly differentiated epithelial neoplasm with variably prominent features suggestive of odontogenic histogenesis: a plexiform ribbon architecture, infrequent basilar palisading with antibasilar nuclei, rare basilar cytoplasmic clearing, subepithelial matrix hyalinization, and partial dual cytokeratin-vimentin immunoreactivity. Features of malignancy included regions of necrosis, pronounced cellular atypia, a high mitotic count, extensive tissue invasion and local tissue destruction, and extension of neoplastic cells beyond the margins of the mandibular bone. Collectively, these features are most consistent with mandibular ameloblastic carcinoma. Including our case described here, ameloblastic carcinoma has been reported in only 5 horses. The microscopic features reported most consistently are dual cytokeratin-vimentin immunoreactivity, a high mitotic count, and basilar palisading. Ameloblastic carcinoma should be considered as a differential diagnosis for rapidly growing, locally invasive masses arising from the dentate jaw of horses.

A 3-months old Chinese shar-pei puppy with ichthyosis was investigated. The dog showed generalized scaling, alopecia and footpad lesions. Histopathological examinations demonstrated a non-epidermolytic hyperkeratosis. The parents of the affected puppy did not show any skin lesions. A trio whole genome sequencing analysis identified a heterozygous de novo 3 bp deletion in the KRT1 gene in the affected dog. This variant, NM_001003392.1:c.567_569del, is predicted to delete a single asparagine from the conserved coil 1A motif within the rod domain of KRT1, NP_001003392.1:p.(Asn190del). Immunohistochemistry demonstrated normal levels of KRT1 expression in the epidermis and follicular epithelia. This might indicate that the variant possibly interferes with keratin dimerization or another function of KRT1. Missense variants affecting the homologous asparagine residue of the human KRT1 cause epidermolytic hyperkeratosis. Histologically, the investigated Chinese shar-pei showed a non-epidermolytic ichthyosis. The finding of a de novo variant in an excellent functional candidate gene strongly suggests that KRT1:p.Asn190del caused the ichthyosis phenotype in the affected Chinese shar-pei. To the best of our knowledge, this is the first description of a KRT1-related non-epidermolytic ichthyosis in domestic animals.

Keratins are an integral part of cell structure and function. Here, it is shown that ectopic expression of a truncated isoform of keratin 81 (tKRT81) in breast cancer is upregulated in metastatic lesions compared to primary tumors and patient‐derived circulating tumor cells, and is associated with more aggressive subtypes. tKRT81 physically interacts with keratin 18 (KRT18) and leads to changes in the cytosolic keratin intermediate filament network and desmosomal plaque formation. These structural changes are associated with a softer, more elastically deformable cancer cell with enhanced adhesion and clustering ability leading to greater in vivo lung metastatic burden. This work describes a novel biomechanical mechanism by which tKRT81 promotes metastasis, highlighting the importance of the biophysical characteristics of tumor cells. [ABSTRACT FROM AUTHOR]

Keratins are the main components of the cell cytoskeleton of epithelial cells. Epithelial cells under stressful stimuli react by modifying their keratin expression pattern. Glomerular diseases are pathological conditions that may lead to loss of kidney function if not timely diagnosed and treated properly. This study aims to examine glomerular and tubular keratin expression in podocytopathies, ANCA-associated vasculitis, and IgA nephropathy and how this expression correlates to clinical outcomes. We included 45 patients with podocytopathies (minimal change disease and focal segmental glomerulosclerosis), ANCA-associated vasculitis, and IgA nephropathy, with or without crescentic lesions, and healthy controls. All tissues were assessed by photon microscopy and immunohistochemistry. Biopsy sections were examined for keratins 7, 8, 18, and 19 expression in the glomerular and tubulointerstitial areas separately. Moreover, we examined how keratin expression was correlated with long-term kidney function outcomes. All four studied keratins had significantly increased glomerular expression in patients with ANCA vasculitis compared to controls and MCD patients. Tubular expression of keratins 7, 8, and 19 was related to kidney outcome in all groups. Patients with crescents had higher expression of all keratins in both glomeruli and tubulointerstitium. The presence of tubular atrophy, interstitial fibrosis, mesangial hyperplasia, and interstitial inflammation did not affect keratin expression. Keratins, an abundant component of renal epithelial cells, have the potential to be featured as a biomarker for kidney function prognosis in patients with glomerular diseases. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the differentially expressed proteins (DEP) between high myopia and moderate myopia on the anterior corneal stroma. Methods: Tandem mass tag (TMT) quantitative proteomics was utilized to reveal proteins. DEPs were screened by the multiple change of more than 1.2 times or less than 0.83 and the P value < 0.05. The DEPs were functional annotated by Gene Ontology (GO) terms. Proteins and protein interaction (PPI) networks were conducted with String online tool. Parallel reaction monitoring (PRM) data processing was used to verify the TMT proteomics results. Results: There are 36 DEPs between high myopia and moderate myopia on the anterior corneal stroma, of which 11 proteins are upregulated, 25 proteins are downregulated. The GO analysis demonstrated keratinocyte migration and structural constituent of cytoskeleton that are significantly changed with most of the proteins decreased in high myopic corneas. Keratin 16 (KRT16) and erythrocyte membrane protein band 4.1-like protein 4B are the only two proteins involved in both functions. The PPI analysis showed keratin type II cytoskeletal 6A (KRT6A) and KRT16 that have strong connections. Immunoglobulin lambda variable 8–61(IGLV8-61) and nicotinamide phosphoribosyl transferase (NAMPT) have consistent results with the TMT. Conclusions: The high myopic corneas have 36 DEPs compared to the moderate myopic corneas on the anterior corneal stroma. Keratinocyte migrations and structural constituent of cytoskeleton are weakened in high myopic corneas, which may partly account for the lower corneal biomechanics in high myopic eyes. The lower expressed KRT16 plays important roles in high myopic corneas. [ABSTRACT FROM AUTHOR]

Unlike other epithelial cancer types, circulating tumor cells (CTCs) are less frequently detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients using epithelial marker-based detection approaches despite the aggressive nature of NSCLC. Here, we demonstrate hexokinase-2 (HK2) as a metabolic function-associated marker for the detection of CTCs. In 59 NSCLC patients bearing cytokeratin-positive (CKpos) primary tumors, HK2 enables resolving cytokeratin-negative (HK2high/CKneg) CTCs as a prevalent population in about half of the peripheral blood samples with positive CTC counts. However, HK2high/CKneg tumor cells are a minority population in pleural effusions and cerebrospinal fluids. Single-cell analysis shows that HK2high/CKneg CTCs exhibit smaller sizes but consistent copy number variation profiles compared with CKpos counterparts. Single-cell transcriptome profiling reveals that CK expression levels of CTCs are independent of their epithelial-to-mesenchymal transition (EMT) status, challenging the long-standing association between CK expression and EMT. HK2high/CKneg CTCs display metastasis and EGFR inhibitor resistance-related molecular signatures and are selectively enriched in patients with EGFRL858R driver oncogene mutation as opposed to EGFR19Del , which is more frequently found in patients with prevalent CKpos CTCs in the blood. Consistently, treatment-naïve patients with a larger number or proportion of HK2high/CKneg CTCs in the blood exhibit poor therapy response and shorter progression-free survival. Collectively, our approach resolves a more complete spectrum of CTCs in NSCLC that can potentially be exploited to identify patient prognosis before therapy.

The changes in endometrial cells, both in the eutopic endometrium of patients with and without endometriosis and in lesions at ectopic sites, are frequently described and often compared to tumorigenesis. In tumorigenesis, the concept of “seed and soil” is well established. The seed refers to tumor cells with metastatic potential, and the soil is any organ or tissue that provides a suitable environment for the seed to grow. In this systematic review (PRISMA-S), we specifically compared the development of endometriosis with the “seed and soil” hypothesis. To determine changes in the endometrial seed, we re-analyzed the mRNA expression data of the eutopic and ectopic endometrium, paying special attention to the epithelial–mesenchymal transition (EMT). We found that the similarity between eutopic endometrium without and with endometriosis is extremely high (~99.1%). In contrast, the eutopic endometrium of patients with endometriosis has a similarity of only 95.3% with the ectopic endometrium. An analysis of EMT-associated genes revealed only minor differences in the mRNA expression levels of claudin family members without the loss of other cell–cell junctions that are critical for the epithelial phenotype. The array data suggest that the changes in the eutopic endometrium (=seed) are quite subtle at the beginning of the disease and that most of the differences occur after implantation into ectopic locations (=soil).

Background: Lung adenocarcinoma (LUAD) stands as the foremost histological subtype of non-small-cell lung cancer, accounting for approximately 40% of all lung cancer diagnoses. However, there remains a critical unmet need to enhance the prediction of clinical outcomes and therapy responses in LUAD patients. Keratins (KRTs), serving as the structural components of the intermediate filament cytoskeleton in epithelial cells, play a crucial role in the advancement of tumor progression. This study investigated the prognostic significance of the KRT family gene and developed a KRT gene signature (KGS) for prognostic assessment and treatment guidance in LUAD. Methods: Transcriptome profiles and associated clinical details of LUAD patients were meticulously gathered from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The KGS score was developed based on the expression of five prognostic KRT genes (KRT7, KRT8, KRT17, KRT18, and KRT80), and the upper quartile of the KGS score was chosen as the cutoff. The Kaplan-Meier method was evaluated to compare survival outcomes between KGS-high and KGS-low groups. The underlying mechanism was further investigated by GSEA, GSVA, and other bioinformatic algorithms. Results: High expression of the KGS signature exhibited a robust association with poorer overall survival (OS) in the TCGA-LUAD dataset (HR: 1.81; 95% CI: 1.35–2.42, P = 0.00011). The association was further corroborated in three external GEO cohorts, including GSE31210 (HR: 3.31; 95% CI: 1.7–6.47, P = 0.00017), GSE72094 (HR: 1.95; 95% CI: 1.34–2.85, P = 0.00057) and GSE26939 (HR: 3.19; 95% CI: 1.74–5.84, P

Background: In head and neck squamous cell carcinoma (HNSCC), salvage neck dissection (ND) is required after primary chemoradiation in case of residual nodal disease. Upon histopathological examination, viability of tumor cells is assessed but little is known about other prognostic histopathological features. In particular, the presence of swirled keratin debris and its prognostic value is controversial. The aim of this study is to examine histopathological parameters in ND specimens and correlate them with patient outcome to determine the relevant parameters for histopathological reporting. Materials and Methods: Salvage ND specimen from a cohort of n = 75 HNSCC (oropharynx, larynx, hypopharynx) patients with prior (chemo) radiation were evaluated on H&E stains for the following parameters: viable tumor cells, necrosis, swirled keratin debris, foamy histiocytes, bleeding residues, fibrosis, elastosis, pyknotic cells, calcification, cholesterol crystals, multinucleated giant cells, perineural, and vascular invasion. Histological features were correlated with survival outcomes. Results: Only the presence / amount (area) of viable tumor cells correlated with a worse clinical outcome (local and regional recurrence-free survival, (LRRFS), distant metastasis-free survival, disease-specific survival, and overall survival, p < 0.05) in both the univariable and multivariable analyses. Conclusion: We could confirm the presence of viable tumor cells as a relevant negative prognostic factor after (chemo) radiation. The amount (area) of viable tumor cells further substratified patients with worse LRRFS. None of the other parameters correlated with a distinctive worse outcome. Importantly, the presence of (swirled) keratin debris alone should not be considered viable tumor cells (ypN0). [ABSTRACT FROM AUTHOR]

Abstract BLAST searches against the human genome showed that of the 93 keratin-associated proteins (KRTAPs) of Homo sapiens, 53 can be linked by sequence similarity to an H. sapiens metallothionein and 16 others can be linked similarly to occludin, while the remaining KRTAPs can themselves be linked to one or other of those 69 directly-linked proteins. The metallothionein-linked KRTAPs comprise the high-sulphur and ultrahigh-sulphur KRTAPs and are larger than the occludin-linked set, which includes the tyrosine- and glycine-containing KRTAPs. KRTAPs linked to metallothionein appeared in increasing numbers as evolution advanced from the deuterostomia, where KRTAP-like proteins with strong sequence similarity to their mammalian congeners were found in a sea anemone and a starfish. Those linked to occludins arose only with the later-evolved mollusca, where a KRTAP homologous with its mammalian congener was found in snails. The presence of antecedents of the mammalian KRTAPs in a starfish, a sea anemone, snails, fish, amphibia, reptiles and birds, all of them animals that lack hair, suggests that some KRTAPs may have a physiological role beyond that of determining the characteristics of hair fibres. We suggest that homologues of these KRTAPs found in non-hairy animals were co-opted by placodes, formed by the ectodysplasin pathway, to produce the first hair-producing cells, the trichocytes of the hair follicles.

Ceramides are epidermal lipids important for normal skin barrier function. Reduced Ceramide content is associated with atopic dermatitis (AD). House dust mite (HDM) has been localized in AD skin where it plays an exacerbator role. We set to examine the impact of HDM on skin integrity and the effect of three separate Ceramides (AD™, DS, Y30) on HDM-induced cutaneous damage. The effect was tested in vitro on primary human keratinocytes and ex vivo on skin explants. HDM (100 μg/mL) decreased the expression of adhesion protein E-cadherin, supra-basal (K1, K10) and basal (K5, K14) keratins and increased matrix metallopeptidase (MMP)-9 activity. The presence of Ceramide AD™ in topical cream inhibited HDM-induced E-cadherin and keratin destruction and dampened MMP-9 activity ex vivo which was not seen for the control cream or cream containing DS or Y30 Ceramides. The efficacy of Ceramide AD™ was tested in a clinical setting on moderate to very dry skin (as surrogate for environment-induced skin damage). When applied topically for 21 days, Ceramide AD™ significantly reduced transepidermal water loss (TEWL) in patients with very dry skin compared to their TEWL baseline data. Our study demonstrates Ceramide AD™ cream to be effective in restoring skin homeostasis and barrier function in damaged skin and warrants testing in larger clinical trials for possible treatment of AD and xerosis. [ABSTRACT FROM AUTHOR]

Porokeratosis is a rare, acquired or inherited disorder of keratinization characterized by one or more atrophic macules or patches, each surrounded by a characteristic ridge-like hyperkeratotic border. Linear porokeratosis (LP) is a variant of porokeratosis in which the lesions are distributed in a linear way. The skin lesions of linear porokeratosis typically present in infancy or early childhood. However, sometimes they occur in adults. The current work talks about a 13-year-old girl suffering from linear porokeratosis since the age of 2 months. [ABSTRACT FROM AUTHOR]

Oil-secreting sebaceous glands (SGs) are critical for proper skin function; however, it remains unclear how different factors act together to modulate SG stem cells. Here, we provide functional evidence that each SG lobe is serviced by its own dedicated stem cell population. Upon ablating Notch signaling in different skin subcompartments, we find that this pathway exerts dual counteracting effects on SGs. Suppressing Notch in SG progenitors traps them in a hybrid state where stem and differentiation features become intermingled. In contrast, ablating Notch outside of the SG stem cell compartment indirectly drives SG expansion. Finally, we report that a K14:K5→K14:K79 keratin shift occurs during SG differentiation. Deleting K79 destabilizes K14 in sebocytes, and attenuates SGs and eyelid meibomian glands, leading to corneal ulceration. Altogether, our findings demonstrate that SGs integrate diverse signals from different niches and suggest that mutations incurred within one stem cell compartment can indirectly influence another.

The cytoskeleton provides structural integrity to cells and serves as a key component in mechanotransduction. Tensins are thought to provide a force-bearing linkage between integrins and the actin cytoskeleton; yet, direct evidence of tensin's role in mechanotransduction is lacking. We here report that local force application to epithelial cells using a micrometer-sized needle leads to rapid accumulation of cten (tensin 4), but not tensin 1, along a fibrous intracellular network. Surprisingly, cten-positive fibers are not actin fibers; instead, these fibers are keratin intermediate filaments. The dissociation of cten from tension-free keratin fibers depends on the duration of cell stretch, demonstrating that the external force favors maturation of cten-keratin network interactions over time and that keratin fibers retain remarkable structural memory of a cell's force-bearing state. These results establish the keratin network as an integral part of force-sensing elements recruiting distinct proteins like cten and suggest the existence of a mechanotransduction pathway via keratin network.

Defects in keratinocyte transglutaminase (TGM1), resulting in an improper protein scaffold for deposition of the lipid barrier, comprise a major source of autosomal recessive congenital ichthyosis. For that reason, the composition and formation of the cornified (cross-linked) protein envelope of the epidermis have been of considerable interest. Since the isopeptide cross-linked protein components are not individually isolable once incorporated, purified envelopes were analysed by mass spectrometry after trypsin digestion. Quantitative estimates of the identified components revealed some 170 proteins, each comprising at least 0.001% of the total, of which keratins were major constituents accounting for ≈74% of the total. Some prevalent non-keratin constituents such as keratinocyte proline-rich protein, loricrin and late envelope protein-7 were preferentially incorporated into envelopes. The results suggest a model where, as previously observed in hair shaft and nail plate, a diversity of cellular proteins are incorporated. They also help rationalize the minimal effect on epidermis of ablating genes for specific single envelope structural components. The quantitative profile of constituent proteins provides a foundation for future exploration of envelope perturbations that may occur in pathological conditions.

The epidermal growth factor receptor (EGFR) signaling pathway is crucial for skin barrier integrity and immune response. This study explores the impact of EGFR inhibitors, osimertinib and afatinib, on keratinocyte function, focusing on keratin (KRT1, KRT17) and tight junction protein (CLDN1, CLDN2, CLDN4) expression in HaCaT cells. Osimertinib significantly increased the mRNA and protein levels of keratins and inflammatory markers, IL-6 and TNF-α, via activation of the EGFR-STAT3 signaling pathway. Co-treatment with recombinant human EGF reversed these changes, suggesting the pathway's modulatory role. These findings underscore the potential therapeutic applications of targeting the EGFR-STAT3 axis in skin barrier dysfunction and inflammatory skin disorders. [ABSTRACT FROM AUTHOR]

Hair loss condition is heritable and is influenced by multifactorial inheritance. In the present study, spontaneously mutated mice showed hair loss phenotype with defect in the first cycle of hair follicle formation leading to cyclic alopecia. These mutant mice follow autosomal recessive inheritance pattern. The transcriptomic profile and differential gene expression analysis of skin tissues by RNA-sequencing at different stages of hair cycle formation was performed. The genes with significant differential genes expression levels in each stage of hair cycle formation were identified and most of these genes were shown to be associated with keratinization process and hair follicle formation. Transcriptome profiling followed by QPCR validation revealed that mRNA levels of Krt16 , Alox15 , Fetub (upregulated) and Msx2 (downregulated) were significantly differentially expressed in mutant skin tissues during late anagen and catagen stages. Krt6b mRNA and protein levels were significantly higher in the mutant mice during all stages of first hair cycle formation. The present study provides basis for understanding the differential gene expression of hair-related genes, including keratinization-associated proteins and its relevance. These mutant mice can serve as a model for studying hair loss condition that can be further used in the identification, evaluation and treatment strategies for alopecia condition. First hair cycle formation in wildtype and hair loss mice: First hair cycle formation in mice occurs from late embryogenesis and this anagen phase continues till postnatal day P17. Once hair follicle is formed, it undergoes regression during catagen phase (P18 to P20). Further hair follicle enters into resting phase (P1 to P29) where the hair follicle stem cells gain regenerative capacity to further enter into anagen phase. In spontaneously mutated inbred mice that gained hairloss phenotype, first phase of anagen is normal but the catagen phase is delayed due to which hair follicle formation gets affected leading to hairloss condition. RNA sequencing analysis indicated abnormal expression of Krt16 and Krt6b mRNA levels in hairloss at all phases. Delayed catagen entry can be attributed low Msx2 and high Alox15 protein levels in hairloss mice. [Display omitted] • Spontaneously mutated inbred mice show late entry into catagen phase of hair cycle. • Catagen entry delay and abnormal expression of Alox15 and MSX2 led to hairloss. • Abnormal expression KRT6b levels observed in hairloss mice at all haircycle stages. [ABSTRACT FROM AUTHOR]

Epidermal keratinocytes undergo cornification to form the cellular building blocks of hard skin appendages such as nails and the protective layer on the surface of the skin. Cornification requires the cross-linking of structural proteins and the removal of other cellular components to form mechanically rigid and inert corneocytes. Autophagy has been proposed to contribute to this intracellular remodelling process, but its molecular targets in keratinocytes, if any, have remained elusive. Here, we deleted the essential autophagy factor Atg7 in K14-positive epithelia of mice and determined by proteomics the impact of this deletion on the abundance of individual proteins in cornified nails. The genetic suppression of autophagy in keratinocytes resulted in a significant increase in the number of proteins that survived cornification and in alterations of their abundance in the nail proteome. A broad range of enzymes and other non-structural proteins were elevated whereas the amounts of cytoskeletal proteins of the keratin and keratin-associated protein families, cytolinker proteins and desmosomal proteins were either unaltered or decreased in nails of mice lacking epithelial autophagy. Among the various types of non-cytoskeletal proteins, the subunits of the proteasome and of the TRiC/CCT chaperonin were most strongly elevated in mutant nails, indicating a particularly important role of autophagy in removing these large protein complexes during normal cornification. Taken together, the results of this study suggest that autophagy is active during nail keratinocyte cornification and its substrate specificity depends on the accessibility of proteins outside of the cytoskeleton and their presence in large complexes.

Ectomesenchymal chondromyxoid tumor is a rare and benign neoplasm with a predilection for the anterior dorsal tongue. Despite morphologic heterogeneity, most cases are characterized by a proliferation of bland spindle cells with a distinctive reticular growth pattern and myxoid stroma. The immunophenotype of these neoplasms is likewise variable; most cases express glial fibrillary acid protein and S100 protein, with inconsistent reports of keratin and myoid marker expression. The molecular pathogenesis is poorly understood; however, a subset of cases has been reported to harbor EWSR1 gene rearrangement. Following identification of an RREB1-MKL2 fusion gene by RNA Sequencing in an index patient, a retrospective review of additional cases of ectomesenchymal chondromyxoid tumors was performed to better characterize the clinical, immunohistochemical, and molecular attributes of this neoplasm. A total of 21 cases were included in this series. A marked predisposition for the dorsal tongue was confirmed. Most cases conformed to prior morphologic descriptions; however, hypercellularity, hyalinized stroma, and necrosis were rare attributes not previously emphasized. The neoplastic cells frequently coexpressed glial fibrillary acid protein, S100 protein, keratin, smooth muscle actin, and/or desmin; a single case was found to contain significant myogenin expression. An RREB1-MKL2 fusion product was identified in 19 tumors (90%), a single tumor (5%) had an EWSR1-CREM fusion product, and the remaining case lacked any known fusion gene by RNA Sequencing. The latter 2 cases subtly differed morphologically from many in the cohort. This series illustrates that recurrent RREB1-MKL2 fusions occur in most, perhaps all, cases of ectomesenchymal chondromyxoid tumor.

Advances in mass spectrometry-based proteomics now permit analysis of complex cellular structures. Application to epidermis and its appendages (nail plate, hair shaft) has revealed a wealth of information about their protein profiles. The results confirm known site-specific differences in levels of certain keratins and add great depth to our knowledge of site specificity of scores of other proteins, thereby connecting anatomy and pathology. An example is the evident overlap in protein profiles of hair shaft and nail plate, helping rationalize their sharing of certain dystrophic syndromes distinct from epidermis. In addition, interindividual differences in protein level are manifest as would be expected. This approach permits characterization of altered profiles as a result of disease, where the magnitude of perturbation can be quantified and monitored during treatment. Proteomic analysis has also clarified the nature of the isopeptide cross-linked residual insoluble material after vigorous extraction with protein denaturants, nearly intractable to analysis without fragmentation. These structures, including the cross-linked envelope of epidermal corneocytes, are comprised of hundreds of protein constituents, evidence for strengthening the terminal structure complementary to disulphide bonding. Along with other developing technologies, proteomic analysis is anticipated to find use in disease risk stratification, detection, diagnosis and prognosis after the discovery phase and clinical validation.

1. The objective of this study was to examine the keratin composition of crop milk, the variation of epithelial thickness and keratin (K) gene expression in samples from young pigeon during incubation and chick rearing. 2. Crop milk was collected from 1-, 3- and 5-day-old squab crops for keratin content analysis. Results showed that K4 accounted for the highest proportion of all detected keratins. 3. In total, 42 pairs of adult pigeons were allocated to seven groups according to different stages to collect crop samples. Gene expression studies showed that the K3 gene expression was maximised at rearing Day 15 (15) and R1 in males and females, respectively. K6a gene level was the greatest at R15 in females, whereas it peaked at incubation Day 4 (I4) in males. The K12, K13, K23 and K80 gene levels were inhibited at the peak period of crop milk formation in comparison with I4. In females, K cochleal expression peaked at I10, whereas it was the greatest at R25 in males. K4 and K14 gene expression was the highest at I10 in females, while K4 and K14 were minimised at I17 and R7 in males, respectively. Gene expressions of K5, K8, K19 and K20 in males and K19 in females were maximised at R1. The K5, K20 and K75 gene levels in females peaked at R7. K75 and K8 expressions in males and females reached a maximum value at R25 and I17, respectively. 4. The epithelial thickness of male and female crops reached their greatest levels at R1 and had the highest correlation with K19. 5. These results emphasised the importance of keratinisation in crop milk formation, and different keratins probably play various roles during this period. The K19 was probably a marker for pigeon crop epithelium development. The sex of the parent pigeon affected keratin gene expression profiles. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the wound healing of recipient and donor sites following keratinized mucosa augmentation (KMA) around implants in reconstructed jaw areas and to compare these outcomes with gingival grafts in native jawbone, so as to provide clinical guidance for postoperative maintenance, and to investigate the impact of clinical experience on the evaluation of KMA postoperative healing through subgroup comparisons., Methods: This study included patients who underwent resection of maxillofacial tumors, fibular or iliac flap reconstruction, and implant placement at Peking University Dental Hospital from October 2020 to April 2023. Three months post-implant placement, the patients were referred for KMA procedures. Clinical photographs of the reconstructed area were taken preoperatively, immediately postoperatively, and 3 weeks and 3 months post-surgery. Additionally, photographs of the palatal donor site were obtained preoperatively and 3 weeks later. Wound healing was assessed by four junior and three senior clinicians utilizing the early healing index (EHI), early wound healing score (EHS), and pink esthetic score (PES).And senior clinicians evaluated the healing effect compared with gingival transplantation on natural jawbone using a 10-point scale., Results: A total of 26 patients with jawbone reconstruction were included, with an average age of (34.2±10.2) years, 11 males (42.3%) and 15 females (57.7%). Among them, 13 cases (50.0%) underwent fibula flap reconstruction, and 13 cases (50.0%) underwent iliac flap reconstruction. The average number of implants per patient was 3.2±0.7. In the recipient area, 3 weeks postoperatively, the EHS was 7.0 (4.0, 9.0), with sub-item scores as follows: Clinical signs of re-epithelialization (CSR) 6.0 (3.0, 6.0), clinical signs of haemostasis (CSH) 1.5 (1.0, 2.0), and clinical signs of inflammation (CSI) 1.0 (0.0, 1.0), indicating that the average appearance of the wound in the recipient area was characterized by generally well-approximated wound edges with minimal fibrin lines and mild erythema and swelling. The EHI for the recipient area was 2.0 (1.5, 2.5), suggesting that the incision was mostly closed with some fibrin lines 3 weeks postoperatively. The long-term healing evaluation system, PES, was 2.5 (2.0, 3.0), with sub-scores for color [1.0 (1.0, 1.5)] and texture [1.5 (1.0, 2.0)], which were slightly different from the reference values.In the palatal donor area, 3 weeks postoperatively, the EHI score was lower at 1.3 (1.0, 2.5), while the EHS score was higher at 8.5 (6.0, 10.0), indicating better soft tissue healing in the donor area compared with the recipient area. Among the clinicians with different levels of experience, the assessment of wound healing revealed that except for the CSI sub-item, where the junior group scored higher than the senior group, all other sub-items showed significantly higher scores in the senior group compared with the junior group. In the EHS evaluation system, the CSH sub-item demonstrated no significant differences between the groups with varying levels of experience. Experienced clinicians' evaluation outcomes of healing effect compared with gum graft on natural alveolar bone was 8.5 (7.5, 9.5), showing high consistency [intraclass correlation coefficient (ICC): 0.892; 95% confidence interval ( CI ): 0.791－0.949], suggesting slightly suboptimal healing results after KMA surgery., Conclusion: The healing process following KMA in the context of jawbone reconstruction is relatively protracted, emphasizing the necessity for comprehensive postoperative management. Moreover, clinician experience plays a significant role in the assessment of wound healing outcomes for KMA in maxillofacial reconstruction.

Purpose: To assess the alteration in keratinized mucosa (KM) dimensions during the early healing period after implant placement and the influence of the variables measured during implant surgery on KM alteration., Materials and Methods: The study participants were consecutively recruited from patients who had received implants following a nonsubmerged surgical protocol. The implant had to be placed in an extraction socket that had healed for more than 6 months without any soft or hard tissue augmentation. Keratinized mucosa width (KMW), keratinized mucosa thickness (KMT), soft tissue level (STL), and probing pocket depth (PPD) were all measured at implant placement as well as at 3 and 6 months after implant surgery. The influence of these variables measured during implant surgery on the 6-month KMW alteration was assessed., Results: A total of 66 implants in 55 patients who completed the follow-up examination after 6 months were included in this study. KMW, KMT, and STL significantly decreased at the 3- and 6-month follow-ups by 0.7 to 1.2 mm. KMW decreased by 24.6%. Mesial PPD significantly increased between the 3- and 6-month follow-ups. In the multivariate generalized estimating equations (GEE) analysis, the implant diameter negatively influenced KMW alteration at the 6-month follow-up, but the KMW at implant surgery was positively influenced at the 6-month KMW alteration follow-up., Conclusions: The KMW decreased significantly at the 3- and 6- month follow-ups after implant placement. If the initial KMW was wider, the KMW decreased more at 6 months after implant placement. Therefore, it is important to carefully monitor KMW alterations during the early healing period to ensure optimal esthetics and peri-implant tissue health.

Objectives: To compare the 5-year outcomes of collagen matrix (CM) and free gingival graft (FGG) used to augment the keratinized mucosa (KM) around posterior dental implants., Materials and Methods: Thirty patients (44 implants) with inadequate KM (< 2 mm) on posterior dental implants were randomized into two groups that received KM augmentation with CM or FGG. Clinical measurements comprising the KM width (KMW), buccal mucosal thickness (MT), and clinical parameters were examined in a 5-year follow-up. Marginal bone loss (MBL) was evaluated with standardized radiographs using the paralleling technique. Patient-reported outcomes (PROs) during the first week post-surgery and at the 5-year follow-up were evaluated., Results: KMW increased significantly during the follow-up period in both groups. The FGG group had a significantly greater KMW than the CM group at the 1, 2-month follow-up and after the 6-month follow-up. KM shrinkage was observed, and was greatest within the first 2 months post-surgery in both groups. At the 5-year follow-up, the KM shrinkage was significantly different between the groups (FGG: 47%; CM: 70%) (p < 0.01). The MT increased significantly in the FGG group. The clinical parameters and MBL were similar between the groups. The bleeding score in the FGG group was higher than that in the CM group (p < 0.05) within the first 2 days post-surgery, while other PROs scores were similar between groups in the first week post-surgery. At 5-year follow-up, all patients were highly satisfied with the treatments., Conclusions: FGG was superior to CM in terms of the KM augmentation and MT increase. Except for a slight difference in self-reported bleeding during the first two post-operative days, CM didn't demonstrate other significant advantages in PROMs., Trial Registration: ChiCTR1800018285 (date of registration: 9/9/2018, retrospectively registered. URL: https://www.chictr.org.cn/showproj.html?proj=24156)., (© 2024 Wiley Periodicals LLC.)

Objectives: Successful implant therapy must also ensure the integration of the soft tissues around the crown/abutment emergence profile. The existing literature does not consistently agree on the necessity of a minimal amount of keratinized tissue (KT), though it appears advantageous for the long-term stability and aesthetics of implants. The purpose of this clinical retrospective study is to compare the effectiveness of amnion/chorion membrane and autogenous subepithelial connective tissue in increasing the keratinized mucosa and maintaining it over a 5-year follow-up., Methods: Twenty patients who had previously undergone implant surgery were included in the study. Ten patients had received the allograft (Group 1) and ten had received autogenous connective tissue (Group 2).An independent examiner retrospectively analyzed the patient records at 7, 15, and 60 days, and five years post-procedure. Data from these observations were collected and analyzed using SPSS Statistics, version 25. Descriptive statistical analysis was conducted., Results: All patients exhibited an increase in KT. For Group 1, the mean KT width measurements were 1.27 ± 0.46 mm at the initial evaluation, increasing to 2.00 ± 0.38 mm, 2.80 ± 0.78 mm, 3.27 ± 0.80 mm, and 3.01 ± 0.68 mm at 7, 15, and 60 days post-surgery (with prosthesis delivery on day 60), and five years after prosthetic rehabilitation, respectively., Conclusions: Within the limitations of this retrospective clinical study, both amnion/chorion and connective tissue show significant potential for KT expansion when used in conjunction with implant surgery., Clinical Relevance: The use of allografts, due their low morbidity, and acceptable results should be considered as a viable option for soft tissues augmentations., Competing Interests: Declarations. Institutional review board statement: This study followed the Declaration of Helsinki with regard to medical protocol and ethics, and the University of Genoa Ethical Committee CERA (nr. 2024/64). Informed consent statement: Informed consent was obtained from all subjects involved in the study and written informed consent has been obtained from the patient(s) to publish this paper” if applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Melanin pigments block genotoxic agents by positioning on the sun-exposed side of human skin keratinocytes' nucleus. How this position is regulated and its role in genome photoprotection remains unknown. By developing a model of human keratinocytes internalizing extracellular melanin into pigment organelles, we show that keratin 5/14 intermediate filaments mechanically control the 3D perinuclear position of pigments, shielding DNA from photodamage. Imaging and microrheology in human disease-related model identify structural keratin cages surrounding pigment organelles to stiffen their microenvironment and maintain their 3D position. Optimum pigment spatialization is required for DNA photoprotection and rely on the interplay between intermediate filaments and microtubules bridged by plectin cytolinkers. Thus, the mechanically-driven proximity of pigment organelles to the nucleus is a key photoprotective parameter. Uncovering how human skin counteracts solar radiation by positioning the melanin microparasol next to the genome anticipates that dynamic spatialization of organelles is a physiological UV stress response., Competing Interests: Competing Interest The authors declare a competing interest. Marion Plessis, Charlène Gayrard, Françoise Bernerd and Christine Duval are full time employees of L’Oreal Research and Innovation, which also provided a financial support through a research contract agreement with Structure and Membrane Compartments’s team, Institut Curie, PSL Research University, CNRS, UMR144, 75005 Paris, France.

Purpose: To compare the effectiveness of keratinized mucosa (KM) augmentation with different techniques for the treatment of dental implants based on risk assessment., Methods: Thirty-nine patients who underwent KM augmentation at implant sites in the posterior mandible were included. Three techniques were used based on anatomy-guided risk assessment: an apically positioned flap (APF) alone, an APF plus a free gingival graft (APF plus FGG), and an APF plus a collagen matrix (APF plus CM). Clinically effective KM augmentation was defined as remaining KM ≥ 2 mm after the intervention. The effective rate, implant/prosthesis survival rates, and bone/soft tissue parameters were analyzed. The correlation between local anatomical characteristics and different techniques was also determined. The associations between the effectiveness of KM augmentation and related factors were analyzed using a linear model., Results: Overall, 74 sites received KM augmentation in the posterior mandible, for an effective rate of 94.6% at the 1-year follow-up and 93.2% at the 5-year follow-up. The KM width in the APF plus FGG group (3.85 ± 1.22 mm) was greater than that in the APF alone (3.05 ± 0.90 mm) (P = 0.016) and APF plus CM (3.21 ± 1.17 mm) groups (P = 0.038) at 5 years post-surgery. There was no significant difference in the effective/ineffective outcomes at the 1-year or 5-year follow-up among the three groups., Conclusions: Comparable effective outcomes were achieved with three KM augmentation techniques following the decision-making criterion based on risk assessment.

Purpose: This study aimed to provide the latest updates on the therapeutic effectiveness of keratinized mucosa (KM) augmentation using autogenous soft tissue grafts for dental implants retaining prostheses., Study Selection: A systematic search of electronic databases was conducted on autogenous soft tissue grafts to create and/or augment KM for functioning dental implants. Two investigators independently extracted data from the selected 11 clinical studies, including 290 participants, from the initially retrieved 573 publications., Results: A lack of KM surrounding dental implants was associated with greater mucosal inflammation. A free gingival graft (FGG) was used to increase the KM width, and a connective tissue graft (CTG) was used to manage peri-implant mucosal recession (MR). The weighted mean gain in KM was 2.6 mm from the selected FGG studies, with a significant reduction in mucosal inflammation and no changes in crestal bone levels for up to 4 years. The weighted mean reduction in MR was 2 mm in selected CTG studies., Conclusions: A lack of KM negatively affects soft tissue health around dental implants. FGG was effective in increasing KM and reducing mucosal inflammation, whereas CTG was effective in decreasing MR.

The present avian anatomists have shown a renewed interest in looking at whether the structure of the avian eyelid is accommodated by the kinetic achievement for each eyelid. The current work utilised both histological and anatomical methods to explore the eyelid's structural association with their kinetic, utilising the hoopoe and cattle egret as natural models. The third lid moved only without implicating other lids. Wrinkles on the edge of the hoopoe's eyelid became less pronounced during the opening phase, in contrast to, the edge of the egret's eyelid. The elevator muscle was visible only in the hoopoe, while both birds possessed the retractor anguli oculi muscles. The two later muscles collaborate with the depressor muscle during the closure phase. Two types of collagen I and III were detected within the stroma of the eyelids of both bird species; the elastic fibres was observed; few were in the hoopoe's eyelids. The eyelid edge of the hoopoe has more of the elastic fibres than those in its eyelid skin. The hoopoe's eyelid's epithelial layers contained more cytokeratin (AE1/AE3) than the egret. In conclusion, the anatomical traits of the hoopoe eyelids contribute to its greater motion compared to the egret eyelids., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Mammalian corneal development is a multistep process, including formation of the corneal epithelium (CE), endothelium and stroma during embryogenesis, followed by postnatal stratification of the epithelial layers and continuous renewal of the epithelium to replace the outermost corneal cells. Here, we employed the Cre- loxP system to conditionally deplete Pax6 proteins in two domains of ocular cells, i.e., the ocular surface epithelium (cornea, limbus and conjunctiva) (OSE) or postnatal CE via K14-cre or Aldh3-cre , respectively. Earlier and broader inactivation of Pax6 in the OSE resulted in thickened OSE with CE and limbal cells adopting the conjunctival keratin expression pattern. More restricted depletion of Pax6 in postnatal CE resulted in an abnormal cornea marked by reduced epithelial thickness despite increased epithelial cell proliferation. Immunofluorescence studies revealed loss of intermediate filament Cytokeratin 12 and diffused expression of adherens junction components, together with reduced tight junction protein, Zonula occludens-1. Furthermore, the expression of Cytokeratin 14, a basal cell marker in apical layers, indicates impaired differentiation of CE cells. Collectively, our data demonstrate that Pax6 is essential for maintaining proper differentiation and strong intercellular adhesion in postnatal CE cells, whereas limbal Pax6 is required to prevent the outgrowth of conjunctival cells to the cornea. [Display omitted] • Transcription factor Pax6 is required for postnatal corneal development. • Pax6-deficient ocular surface ectoderm develops exclusively into conjunctiva. • Conjunctivalisation of the cornea leads to the loss of the limbal region. • Pax6-deficient corneal epithelial cells are defective in intercellular adhesion. • Loss of intercellular adhesion is accompanied by differentiation defects. [ABSTRACT FROM AUTHOR]