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Collodion baby and harlequin ichthyosis
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
D. V. Lakshmi, Sahana M. Srinivas
TGM1 is an enzyme responsible for cross-linking proteins in the cornified cell envelope, and lipoxygenases are a group of dioxygenase enzymes involved in lipid metabolism of lamellar granules or intercellular lipid lamellae in epidermis. Different combinations of TGM1 mutations causing phenotypic variations with respect to severity have also been reported [5]. Ichthyin acts as a receptor for the hepoxilin pathway that leads to abnormalities of the granular layer of the epidermis and abnormal lamellar granules [8]. In a self-healing collodion membrane, compound heterozygous transglutaminase mutation ALOXE3 and ALOX12B genes have been found [10].
Physiological and pathophysiological roles of hepoxilins and their analogs
Published in Drug Metabolism Reviews, 2023
Sara A. Helal, Fadumo Ahmed Isse, Samar H. Gerges, Ayman O. S. El-Kadi
Even though HXs mainly are produced from 12S-LOX, a novel LOX pathway in the normal epidermis was proposed in 2002 by Fischer and his colleagues who provided genetic evidence that established the role of LOX enzymes in the skin (Jobard et al. 2002). The analysis of the catalytic activities of 12 R-LOX and eLOX3 in the skin suggested that they can form HX metabolites (Brash et al. 2007). In addition, biochemical studies using recombinant enzymes found that the biochemical activities of the eLOX3 enzyme exhibit hydroperoxide isomerase activity and can convert 12 R-HpETE to specific hepoxilin-type derivatives (Yu et al. 2003). Genetic mutations of either arachidonate 12-lipoxygenase gene (ALOX12B) which encodes 12 R-LOX enzyme or arachidonate lipoxygenase-3 gene (ALOXE3) encoding eLOX3 enzyme result in deficiency of some HXs and can cause loss of the integrity of the epidermal water barrier. This is greatly associated with a skin disease called ichthyosis which is characterized by severe dehydration, infections, and chronic blistering of the skin (Muñoz-Garcia et al. 2014).
Hypoxia-inducible factor stabilisation-related lncRNAs in retinopathy of prematurity
Published in Journal of Obstetrics and Gynaecology, 2023
Mengkai Du, Zhenghui Cui, Deqin Chen, Yanmin Chen, Zhu Cao, Danqing Chen
Recent evidence has demonstrated that more than 90% of the mammalian genome is transcribed into non-coding RNAs (NcRNAs), which cannot be considered junk or transcriptional noise due to their biological significance (Jathar et al.2017). Most NcRNAs, such as rRNA, tRNA and snoRNA, are smaller than 200 nucleotides (nt). Those longer than 200 nt are called long non-coding RNAs (lncRNAs), which were predicted largely due to the efforts of the FANTOM, GENCODE and the ENCODE consortia (Khorkova et al.2015). These RNAs play important roles in gene expression control in developmental processes, such as dosage compensation, genomic imprinting, cell differentiation and organogenesis (Wu et al.2020, Cai et al.2021). Many reports have shown that lncRNAs located in the nucleus regulate gene expression at the mRNA level in the cytoplasm (Beermann et al.2016). Hung et al. (2011) found that 56 cell-cycle genes harbour lncRNAs and regulate gene expression in human cancers. The expression levels of these genes are regulated by specific oncogenic stimuli, stem cell differentiation or DNA damage (Fatica and Bozzoni 2014). Huarte et al. (2010) found that the inhibition of lncRNA-p21 affects the expression of hundreds of targets genes normally repressed by p53. Tissue differentiation inducing non‑protein coding RNA is a key lncRNA that binds to differentiation mRNAs, including FLG, LOR, ALOXE3, ALOX12B and ABCA12, to ensure their expression (Huarte et al.2010). These examples show that lncRNAs play crucial roles in biological processes (BPs) by targeting mRNAs or other RNAs. Furthermore, lncRNAs have been reported to be associated with many diseases, including cancer, obesity, cardiovascular disease and visual impairment. An improved understanding of the role of lncRNAs in vascular disease may provide new pathophysiological insights, given recent findings on the expression, mechanism and function of lncRNAs implicated in a range of vascular disease states, ranging from those occurring in mice to human subjects (Simion et al.2019). Cissé et al. (2018) expounded the characteristics of lncRNAs and their regulation in glaucoma and Biswas et al. (2019) highlighted some of the key roles of lncRNAs in diabetic retinopathy and inflammation.
Role of Smoking-Mediated molecular events in the genesis of oral cancers
Published in Toxicology Mechanisms and Methods, 2019
In comparison to non smokers, the oral mucosa of smokers shows deregulated expression of numerous protein-coding genes thereby disrupting the oral homeostasis. The tobacco smoke alters the expression of genes involved in following pathways: nicotine signaling (CHRNA3 ↑), xenobiotic metabolism (AHRR ↑, AKR1C1/C2 ↑, CYP1A1↑, CYP1B1 ↑, UGT1A ↑), oxidant stress (ALDH3A1 ↑, GPX2 ↑), eicosanoid synthesis (PTGES ↑, ALOX12B ↑, ALOX15B ↑), and cell adhesion (CEACAM7 ↑), humoral and cell-mediated immune responses (CCL18 ↓), mRNA binding, protection and translocation to cytosol (IGF2BP3 ↓), cell differentiation (SOX9 ↓), cell signaling, and cell-mediated immune response (LEPR ↓) (Boyle et al. 2010; Hussain et al. 2015; Palanichamy et al. 2016; Sumita et al. 2018). In relation to nonsmokers, tobacco smokers have a higher number of mutations in the crucial tumor suppressor gene called p53. The mutations in the p53 gene may result from DNA damage by tobacco smoke carcinogens like PAH and nitrosamines. The p53 mutations and expressional aberrations are among early events culminating to oral carcinogenesis; In India, more than 46% oral cancer cases have mutational inactivated p53 gene (Cruz et al. 1998; Pfeifer et al. 2002; Mishra et al. 2015; Tuna et al. 2019). The normal mucosa of the oral cavity in tobacco smokers shows higher p53 immuno-histological staining than nonsmokers (Zaid et al. 2018). The p53 over-expression associates with oral precancerous and cancer pathologies (Cruz et al. 1998; Gatoo et al. 2018; Zaid et al. 2018). The canonical transcript encoded full length p53 protein (393 amino acids) is functional as the transcription factor regulating apoptosis, DNA repair, cell cycle and cell differentiation (Pfeifer et al. 2002; Hagiwara et al. 2006; Zaid et al. 2018). The p53 isoforms encoded by non–canonical transcripts are functional with malignant lesions posing tumor progressive role (contradictory to the canonical isoform) (Surget et al. 2014; Li and Zhang 2015; Jo et al. 2016). Following Ensembl, p53 gene has more than twenty non-canonical protein-coding transcript variants which may have either tumor promoting or tumor suppressive roles; experimental efforts are required to reveal the functional roles of p53 transcript variants in oral cancer initiation and progression (Zerbino et al. 2018). Survivin, a target gene for canonical p53 protein, encodes protein functional as the inhibitor of apoptosis. Survivin has six transcript variants which are over-expressed in oral cancers and correlate with tumor stage (Mishra et al. 2015).