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To discover vulnerabilities associated with dermokine (DMKN) as a new trigger of the epithelial-mesenchymal transition (EMT) -driven melanoma, we undertook a genome-wide genetic screening using transgenic. Here, we showed that DMKN expression could be constitutively increased in human malignant melanoma (MM) and that this correlates with poor overall survival in melanoma patients, especially in BRAF-mutated MM samples. Furthermore, in vitro, knockdown of DMKN inhibited the cell proliferation, migration, invasion, and apoptosis of MM cancer cells by the activation of ERK/MAPK signaling pathways and regulator of STAT3 in downstream molecular. By interrogating the in vitro melanoma dataset and characterization of advanced melanoma samples, we found that DMKN downregulated the EMT-like transcriptional program by disrupting EMT cortical actin, increasing the expression of epithelial markers, and decreasing the expression of mesenchymal markers. In addition, whole exome sequencing was presented with p.E69D and p.V91A DMKN mutations as a novel somatic loss of function mutations in those patients. Moreover, our purposeful proof-of-principle modeled the interaction of ERK with p.E69D and p.V91A DMKN mutations in the ERK-MAPK kinas signaling that may be naturally associated with triggering the EMT during melanomagenesis. Altogether, these findings provide preclinical evidence for the role of DMKN in shaping the EMT-like melanoma phenotype and introduced DMKN as a new exceptional responder for personalized MM therapy. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the most common gynecological malignant tumors worldwide, for which chemotherapeutic strategies are limited due to their non-specific cytotoxicity and drug resistance. The natural product thymoquinone (TQ) has been reported to target a vast number of signaling pathways in carcinogenesis in different cancers, and hence is regarded as a promising anticancer molecule. Inhibition of epithelial to mesenchymal transition (EMT) regulators is an important approach in anticancer research. In this study, TQ was used to treat the cervical cancer cell lines SiHa and CaSki to investigate its effects on EMT-regulatory proteins and cancer metastasis. Our results showed that TQ has time-dependent and dose-dependent cytotoxic effects, and it also inhibits the migration and invasion processes in different cervical cancer cells. At the molecular level, TQ treatment inhibited the expression of Twist1, Zeb1 expression, and increased E-Cadherin expression. Luciferase reporter assay showed that TQ decreases the Twist1 and Zeb1 promoter activities respectively, indicating that Twist1 and Zeb1 might be the direct target of TQ. TQ also increased cellular apoptosis in some extent, but apoptotic genes/proteins we tested were not significant affected. We conclude that TQ inhibits the migration and invasion of cervical cancer cells, probably via Twist1/E-Cadherin/EMT or/and Zeb1/E-Cadherin/EMT, among other signaling pathways. [ABSTRACT FROM AUTHOR]

The umbilical cord (UC) is vital to maintain blood circulation between the mother and the growing fetus, which is sometimes disrupted. The umbilical artery thrombosis (UAT) is an infrequent complication of pregnancy that can lead to extreme perinatal outcomes, ranging from intrauterine growth restriction stillbirth to neonatal death. The prenatal diagnosis of UAT is essential and sometimes challenging to detect in clinical practice. Once it is detected, the emergent delivery through a cesarean section is considered after the steroidal lung maturity of the fetus. We report a primigravida diagnosed with this rare pregnancy complication, the UAT at delivery, along with the nuchal cord and abnormally coiled UC. The patient had an uneventful course of pregnancy except for the premature rupture of membranes and continuous fetal distress in the second stage of labor. As the labor progression was optimal, and prioritizing the patient's desire, she was vigilantly observed under the premise of continuous electronic fetal monitoring (EFM) to facilitate any emergency, ultimately resulting in the spontaneous vaginal delivery of an alive and healthy baby boy. The fetal distress detected through EFM is an indicator of several stressors predisposing the fetus to some unknown danger that carries an increased risk of perinatal mortality. Based on our experience, it is suggested that radiologists should routinely conduct UC sonographic studies on regular antenatal scans; obstetricians should also have a brief and precise awareness of the critical lifesaving sonographic parameters to measure. The UAT, nuchal cord, and abnormal UC coiling, as found in our case, are all rare factors and related to some extent of fetal morbidity and mortality; once such complications are prenatally suspected, one should manage it through close monitoring and timely decision of appropriate delivery time., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Li et al.)

Choroideremia (CHM) is a rare form of X-linked chorioretinal dystrophy that is caused by mutations in the CHM gene. Mutations in the Rab escort protein-1 (REP-1), an ubiquitously encoded protein of the CHM gene, lead to prenylation and vesicle trafficking deficiency in the protein, resulting in the progressive degeneration of choriocapillaris, retinal pigment epithelium (RPE), and photoreceptors. Despite previous studies concerning this disease, no effective diagnostic tests or established therapeutic interventions currently exist for CHM. In this paper, we reviewed ‎the pathogenic ‎effects of synonymous hotspot mutation in the CHM gene and the genotypic-phenotypic associations in families with CHM. In addition, we employed a combination of molecular dynamics simulations and principal component analysis to gain insight into the underlying molecular basis of these deleterious and disease-causing hotspot mutation ‎analogs. These computer predictions provide strong evidence that the C > T nonsynonymous hotspot mutations of CHM spectrum contribute to overall RPE retinopathy. These findings increase our understanding of the CHM ‎pathogenesis, which may potentially define a new approach in developing novel symbiotic strategies for genetic diagnosis and specific treatment of inherited retinal diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)