Expression Of Cytokeratin Research Articles

Different expression patterns of p63 and p73 in Felis catus papillomavirus type 2-associated feline Merkel cell carcinomas and other epidermal carcinomas.

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine tumor, and more than 90% of feline MCC cases test positive for Felis catus papillomavirus type 2 (FcaPV2). In the present study, basal cell markers p40, p63, and p73 and the stem cell marker SOX2 and cytokeratin 14 (CK14) were immunohistochemically examined in normal fetal, infant, and adult feline skin tissues. The expression of these proteins was examined in tumors positive for FcaPV2, including MCC, basal cell carcinoma (BCC), Bowenoid in situ carcinoma (BISC), and squamous cell carcinoma (SCC). Infant and adult feline skin tissues had mature Merkel cells, which were CK14-, CK18+, CK20+, SOX2+, synaptophysin+ and CD56+, while fetal skin tissue had no mature Merkel cells. MCC was immunopositive for p73, CK18, and SOX2 in 32/32 cases, and immunonegative for CK14 in 31/32 cases and for p40 and p63 in 32/32 cases. These results indicate that MCC exhibits different immunophenotypes from Merkel cells (p73-) and basal cells (p40+, p63+, and SOX2-). In contrast, all 3 BCCs, 1 BISC, and 2 SCCs were immunopositive for the basal cell markers p40, p63, and p73. The life cycle of papillomavirus is closely associated with the differentiation of infected basal cells, which requires the transcription factor p63. Changes in p63 expression in FcaPV2-positive MCC may be associated with unique cytokeratin expression patterns (CK14-, CK18+, and CK20+). Furthermore, SOX2 appears to be involved in Merkel cell differentiation in cats, similar to humans and mice.

Evaluation of the effect of injectable platelet-rich fibrin (i-PRF) in wound healing and growth factor release in rats: a split-mouth study

This experimental study aimed to evaluate the effects of injectable platelet-rich fibrin (i-PRF) on mucosal healing and the release of growth factors in rats. 40 rats were used; i-PRF was administered in the right buccal area while saline was injected in the left. Cytokeratin, FGF, PDGF, TGF, and VEGF expressions were determined with immunohistochemistry. Gene expressions of EGF, TGF-β, and VEGF were analysed. Epithelialization started on the 3rd day, and connective tissue maturation was more prominent in the i-PRF-applied group. Also, the releases of VEGF, EGF, TGF-β, PDGF, and FGF were higher in the i-PRF group during the 14 days. Gene expression analysis showed that changes in TGF-β at 14 days after i-PRF injection and VEGF after 21 days were statistically significant. The results of this study suggested that autologous i-PRF application enhanced the healing of oral mucosal wounds by increasing the release of growth factors for 21 days.

Fusion expression, purification, and characterization of cytokeratin 19 fragments in E. coli for enhanced stability in diagnostic applications

Cytokeratin 19 fragment (CYFRA21-1) serves as a crucial tumor marker in the context of lung cancer patients, playing a pivotal role as a calibrator in the realm of in vitro diagnostics. Nevertheless, during practical application, it has come to light that the recombinantly synthesized full-length CYFRA21-1 antigen exhibits suboptimal stability at the requisite concentration, while the utilization of natural antigens incurs a substantial cost. To address this issue, our investigation harnessed a strategic approach whereby the soluble fragment of cytokeratin 19 (Aa244-400) was integrated into the pET32a vector, subsequently being expressed within E. coli through a fusion with the TrxA protein. This process involved induction of protein expression through 0.2 mM IPTG at 16 °C for a duration of 16 h. After induction, the target protein was purified through Ni affinity and ion exchange chromatography. Subsequent characterization of the targeted protein was executed through the SEC-HPLC technique. The attained CYFRA21-1 antigen, as generated within this study, was effectively incorporated into a chemiluminescence-based in vitro diagnostic detection kit. The results indicate that the fusion protein exhibited commendable reactivity and stability, manifesting a deviation of less than 10 % following incubation at 37 °C for 7 days. Importantly, the production yield achieved a notable magnitude of 300 mg/L, thus rendering it a cost-effective and scalable alternative to natural antigens for clinical diagnostic applications.

Modeling Molecular Pathogenesis of Idiopathic Pulmonary Fibrosis-Associated Lung Cancer in Mice.

This characterization of tumors associated with lung diseases provides new therapeutic targets that may aid in the development of treatment paradigms for lung cancer patients with preexisting pulmonary diseases.

Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review.

A growing body of literature suggests that the expression of cytokeratin 17 (K17) correlates with inferior clinical outcomes across various cancer types. In this scoping review, we aimed to review and map the available clinical evidence of the prognostic and predictive value of K17 in human cancers. PubMed, Web of Science, Embase (via Scopus), Cochrane Central Register of Controlled Trials, and Google Scholar were searched for studies of K17 expression in human cancers. Eligible studies were peer-reviewed, published in English, presented original data, and directly evaluated the association between K17 and clinical outcomes in human cancers. Of the 1705 studies identified in our search, 58 studies met criteria for inclusion. Studies assessed the prognostic significance (n = 54), predictive significance (n = 2), or both the prognostic and predictive significance (n = 2). Altogether, 11 studies (19.0%) investigated the clinical relevance of K17 in cancers with a known etiologic association to HPV; of those, 8 (13.8%) were focused on head and neck squamous cell carcinoma (HNSCC), and 3 (5.1%) were focused on cervical squamous cell carcinoma (SCC). To date, HNSCC, as well as triple-negative breast cancer (TNBC) and pancreatic cancer, were the most frequently studied cancer types. K17 had prognostic significance in 16/17 investigated cancer types and 43/56 studies. Our analysis suggests that K17 is a negative prognostic factor in the majority of studied cancer types, including HPV-associated types such as HNSCC and cervical cancer (13/17), and a positive prognostic factor in 2/17 studied cancer types (urothelial carcinoma of the upper urinary tract and breast cancer). In three out of four predictive studies, K17 was a negative predictive factor for chemotherapy and immune checkpoint blockade therapy response.

Crocin Inhibits Orbital Fibroblasts Fibrosis in Thyroid-Associated Ophthalmopathy

Purpose To investigate the role of Crocin on proliferation, fibrosis, and migration of orbital fibroblasts, as well as the possible signaling pathway. Methods Immunofluorescence assay was performed to detect the expression of fibroblast marker proteins vimentin cytokeratin, desmin, and S-100. The quantity of 5‑ethynyl‑2′‑deoxyuridine-positive cells in orbital fibroblast was analyzed. Quantitative real-time PCR and western blots were performed to evaluate the expression level of fibrosis-related marker including alpha-smooth muscle actin, connective-tissue growth factor, collagen 1A1, and fibronectin. Scratch wound assays were performed to assess wound widths of orbital fibroblast. The expression and phosphorylation of extracellular signal-regulated kinase/signal transducer and activator of transcription 3 were evaluated using western blots. The phosphorylation of smad2 and smad3 was evaluated using immunofluorescence assay. Results Crocin treatment reduced 5‑ethynyl‑2′‑deoxyuridine-positive cells, indicating inhibitory effect on orbital fibroblast proliferation. The expression levels of alpha-smooth muscle actin, connective-tissue growth factor, collagen 1A1 and fibronectin were declined in Crocin treatment. Delayed wound closures were observed in Crocin treatment. Furthermore, Crocin did not affect the expression of extracellular signal-regulated kinase and signal transducer and activator of transcription 3, but weakened extracellular signal-regulated kinase and signal transducer and activator of transcription 3 phosphorylation in orbital fibroblast. The phosphorylation of smad2 and smad3 was attenuated by Crocin as well. Conclusion In conclusion, Crocin inhibits the phosphorylation of extracellular signal-regulated kinase and signal transducer and activator of transcription 3, contributing to the inhibitory effect on proliferation, fibrosis, and migration of orbital fibroblast, suggesting that Crocin has potential to be a novel therapeutic candidate for thyroid-associated ophthalmopathy treatment.

Merkel cell carcinoma as rare malignant skin tumor (two clinical cases)

This article provides a review of the literature on the prevalence of Merkel carcinoma, the features of its clinical, dermoscopic, pathomorphological diagnosis and therapy. In the light of the presented data, two of our own clinical observations of Merkel carcinoma are described: a clinical and dermoscopic description, a pathomorphological and immunohistochemical picture, the treatment performed and its long-term results are given. In the presented clinical observations, Merkel carcinoma was detected in two women aged 70 and 83 years at stage I, which determined a favorable prognosis. Clinically, the tumor was presented in the form of a dense, non-ulcerated nodule or a pink-red nodule; all neoplasms were localized on the head. The dermoscopic picture was different, in one case it was represented by globules and dots of red color against a background of milky pink and white areas, individual linear and convoluted vessels, there were white structures (like chrysalids), and in another case – structureless areas of pink color with tree-like vessels and white structures in the form of chrysalids. Histologically, the small round cell type of structure predominated. An IHC study in both cases revealed a pronounced expression of cytokeratin 20 and chromogranin A, the Ki‑67 index was above 70 %.

Microvascular invasion is associated with poor survival in patients with dual-phenotype hepatocellular carcinoma.

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. 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. 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. Microvascular invasion may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival.

Vulvo-vaginal epithelial tumors in mares: A preliminary investigation on epithelial-mesenchymal transition and tumor-immune microenvironment.

Vulvo-vaginal epithelial tumors are uncommon in mares, and data on the epithelial-to-mesenchymal transition (EMT) and the tumor-immune microenvironment (TIME) are still lacking. This is a study investigating the equus caballus papillomavirus type 2 (EcPV2) infection state as well as the EMT process and the tumor microenvironment in vulvo-vaginal preneoplastic/ benign (8/22) or malignant (14/22) epithelial lesions in mares. To do this, histopathological, immunohistochemical, transcriptomic, in situ hybridization, and correlation analyses were carried out. Immunohistochemistry quantification showed that cytoplasmic E-cadherin and β-catenin expression as well as nuclear β-catenin expression were features of malignant lesions, while benign/preneoplastic lesions were mainly characterized by membranous E-cadherin and β-catenin expression. Despite this, there were no differences between benign and malignant equine vulvo-vaginal lesions in the expression of downstream genes involved in the canonical and noncanonical wnt/β-catenin pathways. In addition, malignant lesions were characterized by a lower number of cells with cytoplasmic cytokeratin expression as well as a slightly higher cytoplasmic vimentin immunolabeling. The TIME of malignant lesions was characterized by more numerous CD204+ M2-polarized macrophages. Altogether, our results support the hypothesis that some actors in TIME such as CD204+ M2-polarized macrophages may favor the EMT process in equine vulvo-vaginal malignant lesions providing new insights for future investigations in the field of equine EcPV2-induced genital neoplastic lesions.

A radiomics model based on magnetic resonance imaging to predict cytokeratin 7/19 expression and liver fluke infection of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. HCC with liver fluke infection could harbor unique biological behaviors. This study was aimed at investigating radiomics features of HCC with liver fluke infection and establishing a model to predict the expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) as well as prognosis at the same time. A total of 134 HCC patients were included. Gadoxetic acid-enhanced magnetic resonance imaging (MRI) images of all patients were acquired. Radiomics features of the tumor were extracted and then data dimensionality was reduced. The radiomics model was established to predict liver fluke infection and the radiomics score (Radscore) was calculated. There were 11 features in the four-phase combined model. The efficiency of the combined model increased significantly compared to each single-phase MRI model. Radscore was an independent predictor of liver fluke infection. It was also significantly different between different expression of CK7/ CK19. Meanwhile, liver fluke infection was associated with CK7/CK19 expression. A cut-off value was set up and all patients were divided into high risk and low risk groups of CK7/CK19 positive expression. Radscore was also an independent predictor of these two biomarkers. Overall survival (OS) and recurrence free survival (RFS) of negative liver fluke infection group were significantly better than the positive group. OS and RFS of negative CK7 and CK19 expression were also better, though not significantly. Positive liver fluke infection and CK19 expression prediction groups harbored significantly worse OS and RFS, survival of positive CK7 expression prediction was unsatisfying as well. A radiomics model was established to predict liver fluke infection among HCC patients. This model could also predict CK7 and CK19 expression. OS and RFS could be foreseen by this model at the same time.

Expression of the cytoskeletal proteins – cytokeratins and beta-III tubulin in human melanoma cell lines from the collection of N. N. Blokhin National Medical Research Center of Oncology

Introduction. Despite advances in the treatment of melanoma, the results of therapy cannot be considered satisfactory, and the search for new drugs and effective combinations of medicine continues. The drugs are being developed aimed at reducing the metastatic tumor potential – migrastatics. The targets of the drugs can be cytoskeletal proteins of tumor cells – cytokeratin (CK) intermediate filaments and microtubule protein beta-III tubulin (TUBB3).Aim. To estimate of the CK and TUBB3 expression in melanoma cell lines to form an informative in vitro cell model for screening and studying migrastatics.Materials and methods. The molecular phenotype of 21 human melanoma cell lines from the collection of N. N. Blokhin National Medical Research Center of Oncology, and 18 of which were isolated from tumor metastases in the lymph nodes, soft tissues or subcutaneously. The level of TUBB3 expression and de novo expression of CKs in vimentin-expressing cells (CK + Vim) were assessed by an immunofluorescent method and flow cytometry.Results. Beta-III tubulin expression was detected in all cultures studied, de novo expression of CKs was found in 20 / 21 lines. The exception was primary uveal melanoma 92-1, that did not express CK + Vim. Both parameters significantly differed between the cells of the studied panel: CK + Vim co-expression – from 0 to 91 %, TUBB3 – from 18 to 86 %. No correlation was found between the expression level of TUBB3 and CK + Vim (Pearson’s correlation coefficient r = 0.11; p = 0.65). Three groups of the cell lines with different ratio of TUBB3 expression and CK + Vim co-expression were identified: 1) similar level of expression of both markers; 2) the level of co-expression of CK + Vim more or less high than the index for TUBB3; 3) the level of TUBB3 expression more or less high than the index for CK + Vim co-expression.Conclusion. A panel of 21 human melanoma cell lines was formed with quantitatively estimated expression of cytoske-letal proteins responsible for the migration activity of tumor cells – CKs and TUBB3. Groups of the lines with different expression ratio of the markers can be used for screening and preclinical evaluation potential migrastatics that reduce the metastatic potential of melanoma and may reduce resistance to taxanes.

Low Molecular Weight Collagen Peptide (LMWCP) Promotes Hair Growth by Activating the Wnt/GSK-3β/β-Catenin Signaling Pathway.

Low molecular weight collagen peptide (LMWCP) is a collagen hydrolysate derived from fish. We investigated the effects of LMWCP on hair growth using human dermal papilla cells (hDPCs), human hair follicles (hHFs), patch assay, and telogenic C57BL/6 mice, while also examining the underlying mechanisms of its action. LMWCP promoted proliferation and mitochondrial potential, and the secretion of hair growth-related factors, such as EGF, HB-EGF, FGF-4, and FGF-6 in hDPCs. Patch assay showed that LMWCP increased the neogeneration of new HFs in a dose-dependent manner. This result correlated with an increase in the expression of dermal papilla (DP) signature genes such as, ALPL, SHH, FGF7, and BMP-2. LMWCP upregulated phosphorylation of glycogen synthase kinase-3β (GSK-3β) and β-catenin, and nuclear translocation of β-catenin, and it increased the expression of Wnt3a, LEF1, VEGF, ALP, and β-catenin. LMWCP promoted the growth of hHFs and increased the expression of β-catenin and VEGF. Oral administration of LMWCP to mice significantly stimulated hair growth. The expression of Wnt3a, β-catenin, PCNA, Cyclin D1, and VEGF was also elevated in the back skin of the mice. Furthermore, LMWCP increased the expression of cytokeratin and Keratin Type I and II. Collectively, these findings demonstrate that LMWCP has the potential to increase hair growth via activating the Wnt/β-catenin signaling pathway.

Electroacupuncture combined with bone marrow mesenchymal stem cell transplantation promotes repair of thin endometrium by regulating SDF-1/CXCR4 signaling

It is to explore, based on stromal cell derived factor 1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signal axis, whether the electroacupuncture (EA) combined with bone marrow mesenchymal stem cells (BMSCs) transplantation can promote thin endometrium regeneration and improve endometrial receptivity, so as to further study its mechanisms underlying improvement of promoting BMSCs homing to repair thin endometrium. Thirty matured female SD rats were randomly divided into normal control , model , BMSCs transplantation (BMSCs), BMSCs+AMD3100 (a specific antagonist of CXCR4, BMSCs+AMD3100), BMSCs+EA, and BMSCs+EA+AMD3100 groups, with 5 rats in each group. The thin endometrial model was established by intrauterine injection of 95% ethanol during the period of estrus. Rats of the model group received intravenous injection of PBS solution (tail vein) on day 1, 3 and 7 of modeling and intraperitoneal injection of normal saline once daily for 3 estrous cycles. Rats of the BMSCs group received intravenous injection of BMSCs suspension on day 1,3 and 7 of modeling, and those of the BMSCs+EA group received BMSCs transplantation and EA stimulation. EA (2 Hz/15 Hz, 1 mA) was applied to "Guanyuan" (CV4) and bilateral "Sanyinjiao"(SP9), "Zigong" (EX-CA1) for 15 min, once daily for 3 estrous cycles. Rats of the BMSCs+AMD3100 group received intravenous injection of BMSCs suspension (1×106/mL) and intraperitoneal injection of AMD3100 (5 mg/kg), and those of the BMSCs+EA+AMD3100 group received administration of BMSCs, AMD3100 and EA, with both groups being once daily for 3 estrous cycles. H.E. staining was used to observe histopathological changes of endometrium tissues, and immunohistochemistry was used to detect the expressions of cytokeratin (CK19) and vimentin in endometrium (for evaluating the damage and repair of endometrium). The expression levels of homeobox A10 (HOXA10), leukemia inhibitory factor (LIF), SDF-1 and CXCR4 proteins were detected by Western blot, and those of SDF-1 and CXCR4 mRNAs in the endometrium detected by real-time PCR. In comparison with the normal control group, the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression leve-ls of HOXA10, LIF and CXCR4 proteins and CXCR4 mRNA were significantly down-regulated (P<0.01), and the expression levels of SDF-1 protein and mRNA significantly up-regulated (P<0.05) in the model group. Compared with the model group, the number of endometrial glands, the immunoactivity of CK19 and vimentin, and the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs group, and the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA, and SDF-1 protein and mRNA in the BMSCs+EA group were significantly up-regulated (P<0.05, P<0.01). Compared to the BMSCs group, the number of endometrial glands, and the expression levels of LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs+EA group were up-regulated (P<0.01, P<0.05)； the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs+AMD3100 group were down-regulated (P<0.01). Compared to the BMSCs+EA group, the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs+EA+AMD3100 group were down-regulated (P<0.01). Results of H.E. staining showed thin endometrium with absence of epithelial cells, and sparse glands and blood vessels, with smaller glandular cavity in the model group, which was relative milder in BMSCs and BMSCs+EA groups. EA can promote the transfer of transplanted BMSCs to the damaged site through SDF-1/CXCR4 signaling related stem cell homing, thereby promoting thin endometrial regeneration, repairing endometrial injury, and improving endometrial tolerance in rats with thin endometrium.

Development of a tissue-engineered skin model with epidermal, dermal and hypodermal components

Tissue-engineered models of skin have evolved over the past 50 years, have successfully been translated to clinical use and continue to be improved using new technologies. However, very few of these constructs incorporate a hypodermal component. The hypodermis is critical to skin homeostasis, skin function and many skin diseases, but our understanding of the hypodermis is limited in comparison to our knowledge of the epidermis and dermis, in part due to a lack of suitable in vitro models.The purpose of this study was to develop and characterise a tissue-engineered model of skin consisting of epidermal, dermal and hypodermal layers, namely a trilayer skin model. Models were produced by culturing human keratinocytes and fibroblasts on decellularised human dermis in combination with explanted human adipose tissue.Bilayer models of skin, comprising of an epidermis and dermis, had a thicker epidermal component compared to trilayer models but exhibited similar cytokeratin expression patterns (AE1/AE3 and cytokeratin 14). Addition of adipose tissue improved the appearance of the dermal-epidermal junction, increased the number of rete ridge-like features and cells maintained similar levels of proliferation (Ki-67) compared to native tissues over 28 days in culture.This technique enabled us to create a physiologically relevant model of human skin with representative morphology across the hypodermis, dermis and epidermis. This model maintained native extracellular matrix architecture, contained a heterogeneous population of cells and has the potential to be applied to a range of different applications where research questions require the inclusion of a hypodermis.

MEF2C and miR-194-5p: New Players in Triple Negative Breast Cancer Tumorigenesis.

Among breast cancer (BC) subtypes, the most aggressive is triple negative BC (TNBC), which is prone to metastasis. We previously found that microRNA (miR)-194-5p is downregulated at the early stages of TNBC brain metastasis development. Additionally, the transcription factor myocyte enhancer factor 2 (MEF2)C, a bioinformatically predicted miR-194-5p target, was increasingly expressed throughout TNBC brain metastasis formation and disease severity. However, the contributions of these two players to malignant cells' features remain undetermined. This study aimed at disclosing the role of miR-194-5p and MEF2C in TNBC tumorigenesis. The transfection of 4T1 cells with a silencer for MEF2C or with a pre-miRNA for miR-194-5p was employed to study TNBC cells' phenotypic alterations regarding epithelial and mesenchymal markers, as well as migratory capability alterations. MEF2C-silenced cells presented a decline in both vimentin and cytokeratin expression, whereas the overexpression of miR-194-5p promoted an increase in cytokeratin and a reduction in vimentin, reflecting the acquisition of an epithelial phenotype. Both treatments reduced TNBC cells' migration. These results suggest that MEF2C may determine TNBC cells' invasive properties by partially determining the occurrence of epithelial-mesenchymal transition, while the overexpression of miR-194-5p promotes a decline in TNBC cells' aggressive behavior and reinforces this miRNA's role as a tumor suppressor in TNBC.

The value of MRI in predicting hepatocellular carcinoma with cytokeratin 19 expression: a systematic review and meta-analysis

To evaluate the overall diagnostic performance of magnetic resonance imaging (MRI), different image features, and different image analysis methods in predicting hepatocellular carcinoma (HCC) with cytokeratin 19 (CK19) expression. A systematic literature search was performed to identify studies using MRI to predict HCC with CK19 expression between 2012 and 2023. Data were extracted to calculate the pooled sensitivity and specificity. Overall diagnostic performance was assessed using areas under the summary receiver operating characteristic curve (AUC). Subgroup analyses were conducted for specific image features and according to image analysis methods (traditional image feature, radiomics, and combined methods). Z-test statistics was used to analyse the differences in diagnostic performance between combined and individual methods. Eleven studies with 14 datasets (1,278 lesions from 1,264 patients) were included. The overall pooled sensitivity, specificity, and AUC with corresponding 95% confidence intervals were estimated to be 0.72 (0.55, 0.85), 0.88 (0.80, 0.93), and 0.89 (0.86, 0.91) for MRI in predicting HCC with CK19 expression. Combined methods had higher sensitivity than image feature methods (0.86 versus 0.54, p=0.001), with no difference in specificity (0.85 versus 0.87, p=0.641). There were no significant differences between radiomics and combined methods regarding sensitivity (p=0.796) and specificity (p=0.535), respectively. MRI shows moderate sensitivity and high specificity in identifying HCC with CK19 expression. The application of radiomics can improve the sensitivity of MRI in identifying HCC with CK19 expression.

Murine Model of Airway Fibrosis has Anatomic, Physiologic, and Molecular Congruency to Human iSGS.

To narrow knowledge gaps in the pathophysiology of idiopathic subglottic stenosis (iSGS) through comparison of a murine subglottic stenosis model with iSGS. In vivo animal study. Academic institution. Murine samples/measurements were obtained from mice that underwent chemomechanical injury with a wire brush and bleomycin. Human samples/measurements were obtained from iSGS patients. Anatomic, physiologic, and epithelial molecular data were collected using histology, human peak expiratory flow (PEF) and murine airway conductance, gene expression analysis with quantitative polymerase chain reaction, and protein analysis with quantitative immunohistochemistry. Anatomic patterns of scars at the subglottis and proximal trachea seen in the murine model are similar to iSGS patients. Subglottic stenosis (SGS) mice had a decrease (P = .0194) in airway conductance compared to healthy controls, similar to a decrease (P = .0001) in predilation PEF versus postdilation in iSGS patients. There was decreased epithelial gene expression of E-cadherin (ECAD) (P < 0.01), occludin (OCLN) (P < .01), and cytokeratin-5 (CK5) (P < .05) and protein expression of ECAD(H/M: P < .001), OCLN (H: P < 0.05, M: P < .001), and CK5 (H: P < .001, M: P < .01) in murine SGS and iSGS versus controls. The murine SGS model shows anatomic, physiologic, and molecular congruency with human iSGS, making it a reasonable model to investigate iSGS. The molecular similarities in epithelial barrier dysfunction suggest it may best be suited to explore epithelial mechanisms of iSGS and therapies directed at epithelial reconstitution. This model provides a foundation to collect data that will improve understanding of iSGS, and, ultimately, translate into more accurate animal models for future use.

Adamantinoma-like ewing sarcoma arising in the pancreatic tail: a case report of a rare entity and review of the literature

ALES is a rare subtype that demonstrates the EWSR1-FLI1 translocation characteristic of ES and demonstrates complex epithelial differentiation including diffuse cytokeratin and p40 expression. It has predominantly recognized in the head and neck and is common in middle-aged population. This case is the first case of ALES reported in the pancreatic tail, sharing some morphological characteristics with ALES in the head and neck, including monotonous cytology, infiltrative growth pattern, and complex epithelioid differentiation, but ALES in the head and neck often has high-grade histological features (e.g., necrosis, high mitotic rate, etc.), and sudden keratinization can also occur, but these features were not reflected in this primary pancreatic tail ALES. Although ALES arising in the pancreatic tail and in the head and neck sites share the immunohistochemical and molecular profile, our case can provide new ideas in differential diagnosis of ALES arising in pancreatic tail and promote increased recognition and understanding of ALES.

Immunohistochemical analysis of cytokeratin 7 and 20 expression in colorectal carcinoma and its correlation with histopathological grading of tumour

Background: Colorectal carcinoma is a malignant epithelial tumor originating in the large bowel. More than 90% of colorectal carcinomas (CRC) are adenocarcinomas. This being graded morphologically at H&amp;E stain in histopathology as well-differentiated, moderately differentiated, and poorly differentiated. Aims and Objectives: The aim of this study is to assess any association with different histopathological types and extent of differentiation of CRC with change in expression of CK 7 and Cytokeratin 20 (CK20). Materials and Methods: In the present study, total 59 patients has been selected by the predetermined sampling techniques. The specimen was collected and the necessary processing was done for H&amp;E stain and for immunohistochemistry for CK 20 and CK 7 profile. Results: This study showed that most of the well-differentiated colorectal carcinoma are CK20 (+ve)/Cytokeratin 7 (CK7) (-ve) and poorly differentiated CRC are CK20 (+) and/CK7 (+) and also CK20 (−ve)/CK7 (+ve). Conclusion: Hence, from this study, it is evident that the expression of CK 20 positivity decreasing and CK7 positivity increasing in respect of progression of well differentiated to poorly differentiated colorectal carcinoma, that is, there is a relationship of expression of CK20 and CK7 profile with the histological grading of colorectal carcinoma. Furthermore, the expression profile of CK20 and CK 7 may be of helpful while searching for unknown primary in cases of metastatic deposit.

A digital light processing 3D-printed artificial skin model and full-thickness wound models using silk fibroin bioink.

A three-dimensional (3D) artificial skin model offers diverse platforms for skin transplantation, disease mechanisms, and biomaterial testing for skin tissue. However, implementing physiological complexes such as the neurovascular system with living cells in this stratified structure is extremely difficult. In this study, full-thickness skin models were fabricated from methacrylated silk fibroin (Silk-GMA) and gelatin (Gel-GMA) seeded with keratinocytes, fibroblasts, and vascular endothelial cells representing the epidermis and dermis layers through a digital light processing (DLP) 3D printer. Printability, mechanical properties, and cell viability of the skin hydrogels fabricated with different concentrations of Silk-GMA and Gel-GMA were analyzed to find the optimal concentrations for the 3D printing of the artificial skin model. After the skin model was DLP-3D printed using Gel-GMA 15% + Silk-GMA 5% bioink, cultured, and air-lifted for four weeks, well-proliferated keratinocytes and fibroblasts were observed in histological analysis, and increased expressions of Cytokeratin 13, Phalloidin, and CD31 were noted in immunofluorescence staining. Furthermore, full-thickness skin wound models were 3D-printed to evaluate the wound-healing capabilities of the skin hydrogel. When the epidermal growth factor (EGF) was applied, enhanced wound healing in the epidermis and dermis layer with the proliferation of keratinocytes and fibroblasts was observed. Also, the semi-quantitative reverse transcription-polymerase chain reaction revealed increased expression of Cytokeratin 13, fibroblast growth factor, and CD31 in the EGF-treated group relative to the control group. The DLP 3D-printed artificial skin model was mechanically stable and biocompatible for more than four weeks, demonstrating the potential for application in skin tissue engineering. STATEMENT OF SIGNIFICANCE: A full-thickness artificial skin model was 3D-printed in this study with a digital light processing technique using silk fibroin and gelatin, which mimics the structural and cellular compositions of the human skin. The 3D-printed skin hydrogel ensured the viability of the cells in the skin layers that proliferated well after air-lifting cultivation, shown in the histological analysis and immunofluorescence stainings. Furthermore, full-thickness skin wound models were 3D-printed to evaluate the wound healing capabilities of the skin hydrogel, which demonstrated enhanced wound healing in the epidermis and dermis layer with the application of epidermal growth factor on the wound compared to the control. The bioengineered hydrogel expands the applicability of artificial skin models for skin substitutes, wound models, and drug testing.