-
Clinical Epigenetics Mar 2022Psoriasis is a chronic and hyperproliferative skin disease featured by hyperkeratosis with parakeratosis, Munro micro-abscess, elongation of rete pegs, granulosa...
BACKGROUND
Psoriasis is a chronic and hyperproliferative skin disease featured by hyperkeratosis with parakeratosis, Munro micro-abscess, elongation of rete pegs, granulosa thinning, and lymphocyte infiltration. We previously profiled gene expression and chromatin accessibility of psoriatic skins by transcriptome sequencing and ATAC-seq. However, integrating both of these datasets to unravel gene expression regulation is lacking. Here, we integrated transcriptome and ATAC-seq of the same psoriatic and normal skin tissues, trying to leverage the potential role of chromatin accessibility and their function in histopathology features.
RESULTS
By inducing binding and expression target analysis (BETA) algorithms, we explored the target prediction of transcription factors binding in 15 psoriatic and 19 control skins. BETA identified 408 upregulated genes (rank product < 0.01) and 133 downregulated genes linked with chromatin accessibility. We noticed that cumulative fraction of genes in upregulation group was statistically higher than background, while that of genes in downregulation group was not significant. KEGG pathway analysis showed that the upregulated 408 genes were enriched in TNF, NOD, and IL-17 signaling pathways. In addition, the motif module in BETA suggested the 57 upregulated genes are targeted by transcription factor AP-1, indicating that increased chromatin accessibility facilitated the binding of AP-1 to the target regions and further induced expression of relevant genes. Among these genes, SQLE, STRN, EIF4, and MYO1B expression was increased in patients with hyperkeratosis, parakeratosis, and acanthosis thickening.
CONCLUSIONS
In summary, with the advantage of BETA, we identified a series of genes that contribute to the disease pathogenesis, especially in modulating histopathology features, providing us with new clues in treating psoriasis.
Topics: Chromatin; DNA Methylation; Humans; Parakeratosis; Psoriasis; Transcription Factor AP-1; Transcriptome
PubMed: 35277199
DOI: 10.1186/s13148-022-01250-6 -
Ear, Nose, & Throat Journal Nov 2022Leukoplakia is a precancerous lesion considered to be within the spectrum of histopathological results from parakeratosis, through stages of dysplasia to invasive... (Review)
Review
INTRODUCTION
Leukoplakia is a precancerous lesion considered to be within the spectrum of histopathological results from parakeratosis, through stages of dysplasia to invasive cancer. Narrow band imaging (NBI) endoscopy has been introduced to improve early diagnosis of benign and malignant laryngeal lesions. The aim of this literature review was to evaluate the accuracy of preoperative evaluation of vocal fold leukoplakia with NBI endoscopy in comparison with histology.
METHODS
A systematic review of the literature was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using 3 different databases: PubMed, Embase, and Scopus. The included articles in the systematic review were identified combining each of the following terms: "narrow band imaging" OR "NBI," [AND] with each of these terms: "laryngeal leukoplakia," OR "vocal fold leukoplakia," OR "vocal cord leukoplakia."
RESULTS
The articles that fully met the inclusion criteria were 5 case series, conducted between January 2010 and February 2018, and published between 2017 and 2019. The selected articles included 312 patients (86% males and 14% females), affected by 382 vocal cord leukoplakia, evaluated with NBI endoscopy and that underwent surgical microlaryngoscopy with biopsy. Based on the studies included in the review, accuracy of NBI in predicting malignancy within leukoplakia ranged from 81% to 97.8%, demonstrating to be an accurate method to predict the risk of malignant transformation of vocal fold leukoplakia.
CONCLUSION
Narrow band imaging can help otolaryngologists in the decision-making process on the necessity to perform a biopsy and transoral surgery or long-term follow-up. Larger studies are necessary to confirm the high association of NBI evaluation of the epithelium surrounding the leukoplakia with the histological diagnosis.
Topics: Endoscopy; Endoscopy, Gastrointestinal; Female; Humans; Laryngeal Neoplasms; Leukoplakia; Male; Narrow Band Imaging; Vocal Cords
PubMed: 33213196
DOI: 10.1177/0145561320973770 -
Journal of Veterinary Diagnostic... Nov 2021Numerous canine papillomaviruses (CPVs) have been identified (CPV1-23). CPV1, 2, and 6 have been associated with inverted papillomas (IPs). We retrieved 19 IPs from 3...
Numerous canine papillomaviruses (CPVs) have been identified (CPV1-23). CPV1, 2, and 6 have been associated with inverted papillomas (IPs). We retrieved 19 IPs from 3 histopathology archives, and evaluated and scored koilocytes, inclusion bodies, giant keratohyalin granules, cytoplasmic pallor, ballooning degeneration, and parakeratosis. IHC targeting major capsid proteins of PV was performed, and CPV genotyping was achieved by PCR testing. Tissue localization of CPV DNA and RNA was studied by chromogenic and RNAscope in situ hybridization (DNA-CISH, RNA-ISH, respectively). IPs were localized to the limbs (50%), trunk (30%), and head (20%), mainly as single nodules (16 of 19). In 15 of 19 cases, immunopositivity was detected within the nuclei in corneal and subcorneal epidermal layers. PCR revealed CPV1 in 11 IPs and CPV2 DNA in 3 IPs. Overall, 14 of 17 cases were positive by both DNA-CISH and RNA-ISH, in accord with PCR results. A histologic score >5 was always obtained in cases in which the viral etiology was demonstrated by IHC, DNA-CISH, and RNA-ISH. IHC and molecular approaches were useful to ascertain the viral etiology of IPs. Although IHC is the first choice for diagnostic purposes, ISH testing allows identification of PV type and the infection phase. RNA-ISH seems a promising tool to deepen our understanding of the pathogenesis of different PV types in animal species.
Topics: Animals; DNA, Viral; Dog Diseases; Dogs; Genotype; In Situ Hybridization; Papilloma, Inverted; Papillomaviridae; Papillomavirus Infections
PubMed: 34338089
DOI: 10.1177/10406387211035799 -
BioRxiv : the Preprint Server For... Dec 2023UBE2N, a Lys63-ubiquitin conjugating enzyme, plays critical roles in embryogenesis and immune system development and function. However, its roles in adult epithelial...
UBE2N, a Lys63-ubiquitin conjugating enzyme, plays critical roles in embryogenesis and immune system development and function. However, its roles in adult epithelial tissue homeostasis and pathogenesis are unclear. We generated conditional mouse models that deleted in skin cells in a temporally and spatially controlled manner. We found that knockout (KO) in the adult skin keratinocytes induced a range of inflammatory skin defects characteristic of psoriatic and actinic keratosis. These included eczematous inflammation, epidermal and dermal thickening, parakeratosis, and increased immune cell infiltration, as well as signs of edema and blistering. Single cell transcriptomic analyses and RT-qPCR showed that KO keratinocytes expressed elevated myeloid cell chemo-attractants such as and and decreased the homeostatic T lymphocyte chemo-attractant, . Consistently, the infiltrating immune cells of -KO skin were predominantly myeloid-derived cells including neutrophils and M1-like macrophages that were highly inflammatory, as indicated by expression of and Pharmacological blockade of the IL-1 receptor associated kinases (IRAK1/4) alleviated eczema, epidermal and dermal thickening, and immune infiltration of the mutant skin. Together, these findings highlight a key role of keratinocyte-UBE2N in maintenance of epidermal homeostasis and skin immunity and identify IRAK1/4 as potential therapeutic target for inflammatory skin disorders.
PubMed: 38105982
DOI: 10.1101/2023.12.01.569631 -
Frontiers in Pharmacology 2021The pathological mechanism of psoriasis and dyslipidemia comorbidity is unclear, and there are few reports on therapy. By establishing an animal model of ApoE mice...
The pathological mechanism of psoriasis and dyslipidemia comorbidity is unclear, and there are few reports on therapy. By establishing an animal model of ApoE mice induced by imiquimod (IMQ), we explored the effects of Liangxue Jiedu formula (LXJDF), a traditional Chinese herb medicine, on psoriasis and dyslipidemia comorbidity through PI3K/Akt/mTOR pathway. The experiment was divided into a control group, a model group, an LXJDF high-dose group, an LXJDF low-dose group, and a positive drug (atorvastatin) group. Each group of mice was given continuous oral administration once a day. After 3 weeks, the mice dorsal skins were smeared with 62.5 mg of 5% IMQ cream for five consecutive days and continued to be given the corresponding drugs. We observed the effects of LXJDF on skin lesion changes, PASI score, pathological characteristics, blood lipid levels (TC, TG, LDL, HDL, and oxLDL), liver pathology, inflammatory factors in the skin, and the protein expression of PI3K/Akt/mTOR pathway in both the skin and liver. The results showed that LXJDF could significantly improve the psoriasiform skin lesions of IMQ-induced ApoE mice, including the reduction of PASI, thinning of epidermal thickness, inhibition of hyperkeratosis and parakeratosis, and inflammatory infiltration in the dermis, and reduce lipid accumulation in the epidermal. LXJDF could regulate blood lipid levels, reduce liver inflammation, and protect the liver. LXJDF could significantly decrease the gene expressions of inflammatory factors IL-17A, IL-23, IL-6, and TNF-α in the skin. LXJDF showed specific inhibition of PI3K, Akt, mTOR protein, and its phosphorylation expressions. In conclusion, LXJDF exerts an intervention effect on psoriasis and dyslipidemia comorbidity PI3K/Akt/mTOR and its phosphorylation pathway.
PubMed: 33762935
DOI: 10.3389/fphar.2021.591608 -
Open Veterinary Journal Jan 2023Bovine papillomatosis (BP) is considered the most common health problem in large cattle farms.
BACKGROUND
Bovine papillomatosis (BP) is considered the most common health problem in large cattle farms.
AIM
This study attempts to confirm clinically suspected BP in cattle by polymerase chain reaction (PCR) assay, histopathology, immunohistochemistry (IHC), and genotyping analysis of local isolates.
METHODS
According to morphological appearance and lesion features, a cross sectional study of 54 clinically diagnosed BP cattle was assigned to this current investigation from May to August (2021) in Al-Kut district (Wasit Province, Iraq) private veterinary clinics using purposive sampling technique based on set criteria. The cattle were diagnosed clinically, and the tissues were collected and some fixed in 10% neutral buffered formalin and other stored frozen and examined by histopathological technique, IHC, and PCR assays.
RESULTS
Using PCR assay, all cattle were positive for the BPV gene. According to detect the gene, analysis of the phylogenetic tree showed that local BPV cattle isolates were closely related to the NCBI-BLAST BPV type-1 and type-2 of the Polish equine isolate (KF284133.1) and BPV Brazilian isolate (MH187961.1), respectively. Histological detection showed there were acanthosis, hyperkeratosis, epidermal thickening, severe infiltration of mononuclear cells, massive hemorrhage, dermal fibroplasias, multifocal spongiosis, moderate neovascularization, moderate to severe elongation of the retention ridge towards the dermis, parakeratosis, rings of calcification, and necrosis with nuclear pyknosis of some spinosum cells. Immunohistochemical findings of tumor necrosis factor-alpha, epidermal growth factor receptor and Fascin showed a significant variation in values of immunoreaction in the dermis and epidermis. These results ranged from negative (0) to mild positive (+1) to moderate positive (+2) reactions.
CONCLUSION
The study provided essential molecular and genotyping data to improve our knowledge by emphasizing the crucial of IHC as an elegant diagnostic method to detect cellular alterations.
Topics: Animals; Cattle; Cattle Diseases; Cross-Sectional Studies; Genotype; Papilloma; Papillomavirus Infections; Phylogeny
PubMed: 36777440
DOI: 10.5455/OVJ.2023.v13.i1.4 -
Cureus Jan 2023A man in his late 70s with a history of psoriasis and non-melanoma skin cancer presented with a progressive rash on his right thenar eminence. He first noticed it about...
A man in his late 70s with a history of psoriasis and non-melanoma skin cancer presented with a progressive rash on his right thenar eminence. He first noticed it about one year ago. He denied any pruritus in the affected region but did note some overlying skin breakdown. He had used topical betamethasone and calcipotriene cream in the past with minimal improvement. Physical examination revealed a pink atrophic plaque with linear hyperkeratotic borders and central fissuring on the right thenar eminence extending into the first webspace. A shave biopsy revealed hypokeratosis with a rim of surrounding hyperkeratosis and associated parakeratosis, basal keratinocyte atypia, and lichenoid inflammation. These histopathological features were consistent with circumscribed palmar hypokeratosis and central actinic keratosis. Circumscribed palmar hypokeratosis is often considered a benign entity, but there have been reports suggesting an association with premalignancy. The decision was made to treat with 5-fluorouracil and calcipotriene cream twice daily for six weeks. At his two-month follow-up, he endorsed a robust reaction, which was further suggestive of premalignant change. He had a near-complete resolution of the rash. This case features circumscribed palmar hypokeratosis and suggests a novel treatment option for patients who develop concomitant actinic keratosis.
PubMed: 36874763
DOI: 10.7759/cureus.34401 -
Frontiers in Immunology 2022To investigate the efficacy of indirubin combined with human umbilical cord mesenchymal stem cells (hUC-MSCs) in the treatment of psoriatic lesions in BALB/c mice and to...
OBJECTIVE
To investigate the efficacy of indirubin combined with human umbilical cord mesenchymal stem cells (hUC-MSCs) in the treatment of psoriatic lesions in BALB/c mice and to explore the related mechanism of indirubin in the treatment of psoriasis.
METHODS
A BALB/c mouse psoriasis model induced by imiquimod was established and randomly divided into the control group, model group, indirubin group, hUC-MSCs group, and indirubin combined with hUC-MSCs group. Psoriasis area and severity index (PASI) score was used to observe skin lesion changes in the psoriasis-like mouse model. The epidermal scale, the degree of keratinization, and the infiltration of inflammatory cells were observed by hematoxylin eosin (HE) staining. The concentrations of TNF-α, IFN-γ, IL-17A, and IL-23 in serum of mice were measured using enzyme-linked immunosorbent assay (ELISA).
RESULTS
The PASI integral trend chart indicates that hUC-MSCs and indirubin and the combination of drugs could relieve the appearance of skin lesions and accelerate the recovery of skin lesions. The indirubin group had the best effect in improving the scale of skin lesions. HE staining showed that the number of parakeratosis cells in the three treatment groups was significantly reduced, the degree of erythrocyte extravasation dermis hyperplasia and inflammatory cell infiltration was significantly lower than that in the model group, and the skin thickness and spleen index of the combined treatment group exhibited the most noticeable improvement. ELISA showed that the concentrations of TNF-α, IFN-γ, IL-17A, and IL-23 in serum of mice in the hUC-MSCs treatment group, indirubin group, and combined administration group were all decreased compared with those in the model group, and the concentrations of IFN-γ, IL-17A, and IL-23 could be decreased significantly in the indirubin group.
CONCLUSIONS
Both hUC-MSCs and indirubin can effectively reduce psoriasis-like lesions in BALB/c mice, and the combined administration of these drugs has the best effect.
Topics: Animals; Mice; Interleukin-17; Interleukin-23; Mesenchymal Stem Cells; Mice, Inbred BALB C; Psoriasis; Skin Diseases; Tumor Necrosis Factor-alpha; Umbilical Cord; Human Umbilical Vein Endothelial Cells; Humans
PubMed: 36466901
DOI: 10.3389/fimmu.2022.1033498 -
Indian Journal of Pathology &... 2022Acquired reactive perforating collagenosis (ARPC), rare disorder characterized by transepidermal elimination (TEE) of collagen fibers, is seen in adult diabetics....
Acquired reactive perforating collagenosis (ARPC), rare disorder characterized by transepidermal elimination (TEE) of collagen fibers, is seen in adult diabetics. Genetic predisposition, familial aggregation, trauma, bites and scratching are implicated. Diabetics develop microvascular diseases leading to intense pruritus causing repeated micro trauma leading to necrosis of connective tissue of dermis, causing TEE. Isolated papules, plaques and nodules with central keratotic plugs, are mostly seen on extensor surfaces of limbs but trunk and face may be involved. Histopathology shows extrusion of abnormal collagen fibers through epidermis. Multiple treatment modalities show variable response. A 52 year old diabetic female had multiple, itchy, well defined, erythematous papules and plaques with central adherent crusting on lower back since 1 month. Histopathology showed cup shaped epidermal depression filled with plug of altered collagen, acanthotic epidermis with hyperkeratosis and parakeratosis. Underlying epidermis was thin with fine slits through which vertically oriented basophilic collagen fibers were extruded.
Topics: Adult; Humans; Female; Middle Aged; Collagen Diseases; Skin Diseases; Epidermis; Diabetes Mellitus; Collagen
PubMed: 36308201
DOI: 10.4103/ijpm.ijpm_333_21 -
Cancers Nov 2023Actinic keratosis (AK), due to its widespread prevalence, as well as the possibility of progression to an invasive form of squamous cell carcinoma, requires treatment...
Actinic keratosis (AK), due to its widespread prevalence, as well as the possibility of progression to an invasive form of squamous cell carcinoma, requires treatment regardless of the clinical stage. New imaging techniques, such as in vivo reflectance confocal microscopy (RCM), significantly increase the accuracy of diagnosis and allow noninvasive evaluation of the therapeutic efficacy of the ongoing treatment. Our objective was to evaluate the prevalence of specific (video)dermoscopy and RCM features of pigmented and classical subtypes of AK before and after photodynamic therapy (PDT) treatment. We included patients with facial grade II AKs (25 pigmented, 275 non-pigmented) were included in the study. Skin lesions were evaluated by (video)dermoscopy and RCM at the baseline and three months after PDT. In classic AK, the most frequent dermoscopic findings were fine wavy vessels (96%), scale (92%), microerosions (48%), and "strawberry" pattern (36%), while pigmented AK was characterized mostly by "rhomboidal pattern" (80%), scale (60%), white globules (48%), "jelly sign", and superficial pigmentation (40%). RCM's most characteristic classic AK findings were abnormal honeycomb pattern in the spinous layer, epidermal inflammatory infiltrate, and solar elastosis that were present in 96% of lesions. Pigmented AKs presented mostly with dark central areas of parakeratosis (72%), mottled pigmentation (72%), dermal inflammatory infiltrate (64%), solar elastosis (60%), and abnormal honeycomb pattern in the spinous layer (56%). Dermoscopically, PDT resulted in complete disappearance of the "rhomboidal pattern" in both classical and pigmented AKs, "starburst pattern" and "jelly sign" in classical AKs, and inner gray halo, "rosette sign" and central crust in pigmented AKs. Three months after one PDT session, RCM evaluation showed mostly solar elastosis in both classical and pigmented AK subtypes, epidermal inflammatory infiltrate in classical AKs, and dermal inflammatory infiltrate in pigmented AKs. New noninvasive imaging techniques such as RCM and (video)dermoscopy can help practitioners better visualize the efficacy of the ongoing PDT treatment in either classical or pigmented AK subtypes.
PubMed: 38067302
DOI: 10.3390/cancers15235598