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International Journal of Molecular... Jun 2023Psoriasis is the most common chronic inflammatory skin disease with a genetic basis. It is characterised by keratinocyte hyperproliferation, parakeratosis and... (Review)
Review
Psoriasis is the most common chronic inflammatory skin disease with a genetic basis. It is characterised by keratinocyte hyperproliferation, parakeratosis and inflammatory cell infiltration. Psoriasis negatively affects a patient's physical and emotional quality of life. Sirtuins (SIRTs; silent information regulators) are an evolutionarily conserved group of enzymes involved in the post-translational modification of proteins, including deacetylation, polyADP-ribosylation, demalonylation and lipoamidation. SIRTs are involved in a number of cellular pathways related to ageing, inflammation, oxidative stress, epigenetics, tumorigenesis, the cell cycle, DNA repair and cell proliferation, positioning them as an essential component in the pathogenesis of many diseases, including psoriasis. Activation of SIRT1 counteracts oxidative-stress-induced damage by inhibiting the mitogen-activated protein kinases (MAPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways and may mitigate pathological events in psoriasis. There is a significant reduction in the expression of SIRT1, SIRT2, SIRT3, SIRT4 and SIRT5 and an increase in the expression of SIRT6 and SIRT7 in psoriasis. The aim of the review is to draw the attention of physicians and scientists to the importance of SIRTs in dermatology and to provide a basis and impetus for future discussions, research and pharmacological discoveries to modulate SIRT activity. In light of the analysis of the mode of action of SIRTs in psoriasis, SIRT1-SIRT5 agonists and SIRT6 and SIRT7 inhibitors may represent new therapeutic options for the treatment of psoriasis.
Topics: Humans; Sirtuin 1; Sirtuins; Quality of Life; Aging; Psoriasis; Skin Diseases
PubMed: 37445960
DOI: 10.3390/ijms241310782 -
CytoJournal 2022Cytology of the uterine cervix is one of the most widely utilized tests and is best known primarily for the cytologic changes seen in precancerous lesions and invasive... (Review)
Review
Cytology of the uterine cervix is one of the most widely utilized tests and is best known primarily for the cytologic changes seen in precancerous lesions and invasive cancer of the uterine cervix. The more common inflammatory conditions of cervicitis and vaginitis are close clinical differentials, especially when they give rise to excessive blood-stained vaginal discharge. These infective conditions also result in variation in the appearance of otherwise benign squamous and glandular cells in cervical cytology specimens. A variety of physiologic and pathologic conditions are responsible for the conversion of polymicrobial flora of the vagina to a monomicrobial one. The latter may overgrow the others and result in inflammation of the cervix and the vagina. Chronic irritation of the cervix due to intrauterine devices, chemical irritants, inflammation/infection, endocrine changes, and reparative changes can lead to worrisome parakeratosis, hyperkeratosis, and squamous metaplasia of non-keratinized squamous mucosa of the cervix and the vagina and may mimic HPV-related changes. Although some benign changes are specific for certain infections, for example, infestation, most of the reactive and hyperplastic cell morphology are important to recognize only due to the significant morphologic overlap with neoplastic changes in cytology specimens. Identification of different pathogens specifically may not be relevant from a clinical point of view, but is undoubtedly a cytologists' privilege to inform the clinician! This chapter describes in detail the cytoplasmic and nuclear reactive changes that are found in specific and non-specific inflammatory conditions. In addition, diagnostic pitfalls are emphasized where necessary.
PubMed: 35673696
DOI: 10.25259/CMAS_03_08_2021 -
Clinical, Cosmetic and Investigational... 2022Granular parakeratosis is an uncommon acquired keratinization disorder that occurs in the armpit, groin, and other parts of the body. It may be related to stimulation by...
Granular parakeratosis is an uncommon acquired keratinization disorder that occurs in the armpit, groin, and other parts of the body. It may be related to stimulation by detergents and antiperspirants. This article reports a case of granular parakeratosis in the groin. The patient was a young man with no predisposing factors. The clinical manifestations included symmetrical bilateral inguinal erythema, dryness, and a small amount of bran-like desquamation. After histopathological examination, the final diagnosis was granular parakeratosis, which was cured by topical application of glucocorticoid cream and silicone oil cream. Granular parakeratosis is a rare skin disease of unknown etiology. Clinicians need to pay attention to this disease and differentiate it from various diseases to avoid misdiagnosis.
PubMed: 35874456
DOI: 10.2147/CCID.S371558 -
Postepy Dermatologii I Alergologii Feb 2021Keratinization means cytodifferentiation of keratinocytes turning into corneocytes in the stratum corneum. Disorders of keratinization (hyperkeratosis, parakeratosis and... (Review)
Review
Keratinization means cytodifferentiation of keratinocytes turning into corneocytes in the stratum corneum. Disorders of keratinization (hyperkeratosis, parakeratosis and dyskeratosis) are causing many dermatological diseases, including various types of ichthyoses, pachyonychia congenita, pityriasis rubra pilaris, all subtypes of psoriasis, pityriasis lichenoides, dyskeratosis congenita, leukoplakia and keratosis follicularis, which apart from skin lesions may affect the eye's adnexae causing ectropion, entropion, blepharitis, madarosis, and trichiasis, the ocular surface causing keratitis, conjunctivitis, corneal ulceration and episcleritis, which in turn cause uveitis and various fundoscopic changes (proliferative retinopathy, retinal vasculopathy, macular oedema and birdshot chorioretinopathy). Knowledge of ocular symtoms associated with pathological keratinization is crucial, preventing sight-threatening complications such as corneal perforation, lagophthalmus, phthisis bulbi, retinal neovascularization, retinal vasculopathy and optic nerve atrophy. This review encourages dermatologists to monitor patients for ocular symptoms and encourage ophthalmologists to monitor patients for dermatological symptoms.
PubMed: 34408561
DOI: 10.5114/ada.2021.104272 -
Dermatopathology (Basel, Switzerland) May 2021Ichthyoses are inborn keratinization disorders affecting the skin only (non-syndromic) or are associated with diseases of internal organs (syndromic). In newborns, they... (Review)
Review
Ichthyoses are inborn keratinization disorders affecting the skin only (non-syndromic) or are associated with diseases of internal organs (syndromic). In newborns, they can be life-threatening. The identification of the gene defects resulted in reclassification and a better understanding of the pathophysiology. Histopathologic patterns include orthohyperkeratosis with a reduced or well-developed stratum granulosum, hyperkeratosis with ortho- and parakeratosis with preserved or prominent stratum granulosum, and epidermolytic ichthyosis. Another pattern features "perinuclear vacuoles and binucleated keratinocytes", which is associated with keratin mutations. Some ichthyoses are histologically defined by psoriasis-like features, and distinct subtypes show follicular hyperkeratosis. In addition to histological and immunohistochemical methods, these patterns allow a better histopathologic diagnosis.
PubMed: 34066992
DOI: 10.3390/dermatopathology8020017 -
Journal of Lower Genital Tract Disease Jul 2022The aim of the study was to evaluate clinicopathologic features of cases demonstrating an acanthotic tissue reaction not clearly consistent with psoriasis, lichen...
OBJECTIVE
The aim of the study was to evaluate clinicopathologic features of cases demonstrating an acanthotic tissue reaction not clearly consistent with psoriasis, lichen simplex chronicus, mycosis, or condyloma.
MATERIALS AND METHODS
This is a retrospective pathologic case series of biopsies reported as "benign acanthotic lesion" and "acanthotic tissue reaction" that lacked a clear diagnosis on expert review. Cases with nuclear atypia were excluded. Clinical and histopathologic data were collected, immunohistochemistry for p16 and p53 were obtained, and molecular testing for 28 common anogenital human papillomavirus (HPV) genotypes was undertaken.
RESULTS
There were 17 cases with a median age of 47 years. Unilaterality and medial location were clinical reasons for diagnostic difficulty. Histopathologic uncertainty often related to lack of papillary dermal fibrosis to support lichen simplex chronicus or psoriasiform lesions without parakeratosis, subcorneal pustules, and/or mycotic elements. Firm pathologic diagnoses were not possible, but 3 groups emerged: favoring chronic dermatitis, favoring psoriasis, and unusual morphologies. p16 results were negative or nonblock positive while p53 was normal or basal overexpressed. Human papillomavirus testing was negative in 12, low positive for HPV 16 in 1, unassessable in 3, and not requested in 1.
CONCLUSIONS
There is a group of acanthotic tissue reactions that cannot be classified with standard histopathologic assessment. Further clinicopathologic research into unilateral acanthotic lesions may provide insight into separation of psoriasis and mycosis when organisms are absent. Once nuclear atypia is excluded, immunohistochemistry for p16 and p53 and HPV molecular testing do not assist in diagnostic identification.
Topics: Alphapapillomavirus; Female; Humans; Middle Aged; Neurodermatitis; Papillomaviridae; Papillomavirus Infections; Psoriasis; Retrospective Studies; Tumor Suppressor Protein p53; Vulvar Neoplasms
PubMed: 35543596
DOI: 10.1097/LGT.0000000000000681 -
Journal of Immunology Research 2020Psoriasis is an immune-mediated inflammatory chronic skin disease characterized by chronic inflammation in the dermis, parakeratosis, and excessive epidermal growth....
BACKGROUND
Psoriasis is an immune-mediated inflammatory chronic skin disease characterized by chronic inflammation in the dermis, parakeratosis, and excessive epidermal growth. MicroRNAs (miRNAs) are key regulators of immune responses. Although differential expression of miRNAs has been reported in certain inflammatory autoimmune diseases, their role in psoriasis has not been fully illuminated. Our aims were to confirm plasma miRNA expression signatures in psoriasis and to examine their potential influence on psoriasis pathogenesis.
METHODS
A miRNome PCR array was used to analyse the plasma of psoriasis patients and healthy donors. We performed miRNA pathway enrichment and target gene network analyses on psoriasis plasma samples.
RESULTS
We found several specific plasma miRNA signatures relevant to psoriasis. The miRNAs targeted pathways associated with psoriasis, such as the VEGF, MAPK, and WNT signaling pathways. Network analysis revealed pivotal deregulated plasma miRNAs and their relevant target genes and pathways regulating psoriasis pathogenesis.
CONCLUSIONS
This study analysed the expression of plasma miRNAs and their target pathways, elucidating the pathogenesis of psoriasis; these results may be used to design novel therapeutic strategies and to identify diagnostic biomarkers for psoriasis.
Topics: Adult; Biomarkers; Circulating MicroRNA; Female; Gene Expression Profiling; Gene Regulatory Networks; Humans; MAP Kinase Signaling System; Male; Middle Aged; Psoriasis; Vascular Endothelial Growth Factor A; Wnt Signaling Pathway
PubMed: 32411787
DOI: 10.1155/2020/1561278