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The Journal of Investigative Dermatology May 2024UBE2N, 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 Ube2n in skin cells in a temporally and spatially controlled manner. We found that Ube2n-knockout (KO) in the adult skin keratinocytes induced a range of inflammatory skin defects characteristic of psoriatic and actinic keratosis. These included 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 Ube2n KO keratinocytes expressed elevated myeloid cell chemo-attractants such as Cxcl1 and Cxcl2 and decreased the homeostatic T lymphocyte chemo-attractant Ccl27a. Consistently, the infiltrating immune cells were predominantly myeloid-derived cells including neutrophils and M1-like macrophages that expressed high levels of inflammatory cytokines such as Il1β and Il24. Pharmacological blockade of the IL-1 receptor associated kinases (IRAK1/4) alleviated inflammation, epidermal and dermal thickening, and immune infiltration of the Ube2n 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: 38796140
DOI: 10.1016/j.jid.2024.04.017 -
Journal of Cutaneous Pathology Dec 2023Cytologic atypia encompasses several features of abnormal cellular morphology. We sought to quantify these features in benign and premalignant/malignant squamous cell... (Observational Study)
Observational Study
BACKGROUND
Cytologic atypia encompasses several features of abnormal cellular morphology. We sought to quantify these features in benign and premalignant/malignant squamous cell lesions to better characterize criteria for malignancy.
METHODS
We conducted a rater-blinded observational study in which histopathology slides were evaluated under light microscopy, and the presence and relative quantity of 24 distinct cytological features were recorded, along with respective diagnoses. Each slide was evaluated, and the ratings were recorded and analyzed.
RESULTS
The most helpful findings, whose presence in high numbers indicates an increased likelihood that the tissue sample is premalignant/malignant, were: (1) pleomorphic parakeratosis; (2) pleomorphic nuclei in the epithelium; (3) irregular nuclei; (4) thick refractile nuclear envelope; (5) presence of nuclear hyperchromasia (dark gray); (6) peripheral nucleoli; and (7) nucleolar stems. Higher values of round or oval nuclear shape and vesicular nuclei increase the likelihood that the tissue sample is benign.
CONCLUSIONS
Certain nuclear features have a higher association with premalignancy/malignancy and may guide histologic evaluation of a given lesion. These findings can be used in combination with architectural features and clinical history to add to a complete diagnostic picture.
Topics: Humans; Cell Nucleus; Precancerous Conditions; Parakeratosis; Carcinoma, Squamous Cell
PubMed: 37730204
DOI: 10.1111/cup.14536 -
European Review For Medical and... Nov 2023Scabies is a skin infestation that has been known for hundreds of years and is caused by the ectoparasitis of Sarcoptes scabiei. Scabies is a public health problem that...
OBJECTIVE
Scabies is a skin infestation that has been known for hundreds of years and is caused by the ectoparasitis of Sarcoptes scabiei. Scabies is a public health problem that can be seen in all age groups, races, genders, socioeconomic groups, and all societies. The aim of this study was to identify the prominent histopathological findings in scabies cases and to guide the clinical approach.
PATIENTS AND METHODS
Scabies cases, which were clinically diagnosed between January 2016 and December 2020 in our hospital, were retrospectively screened, and 3,027 cases were detected. As a result of the screening, a skin punch biopsy-histopathological examination was performed in only 62 cases that were included in the study. Cases without punch biopsy were excluded from the study. After a histopathological evaluation, the cases were divided into two groups: those diagnosed with scabies (n=9) and those diagnosed with nonscabies (n=53). Pathological findings of the groups were statistically compared using Fisher's exact Chi-square test.
RESULTS
After microscopic examination, superficial and deep inflammatory reactions and the presence of lymphocytes were detected in 100% of cases. Furthermore, eosinophils and spongiosis were detected in 55% of cases. Histomorphological findings of the two groups were statistically examined and significant differences were found in spongiosis and eosinophil findings (p=0.019, p=0.025). There were no statistically significant differences in the other histopathological findings (parakeratosis, vesicle, bullae, intraepidermal pustule, vasculitis, dermal edema, superficial and deep inflammatory reaction, neutrophils, and plasma cells - p=0.259, p=0.266, p=0.083, p=0.683, p=0.557, p=0.066, p=0.980, p=0.290, and p=0.083, respectively).
CONCLUSIONS
In histopathological examination of scabies biopsies, spongiosis and eosinophil findings may be useful in differential diagnosis. Pathological diagnosis can be a decisive stage for controlling scabies, which has epidemic potential, especially in crowded environments such as schools, dormitories, and refugee camps. For pathology science to play an active role in the diagnosis of scabies, more punch biopsies are needed from cases. Large-sample prospective clinical studies comparing histopathological findings and the severity of the disease may contribute to the literature.
Topics: Female; Humans; Male; Scabies; Retrospective Studies; Prospective Studies; Skin; Inflammation; Plasma Cells
PubMed: 37975348
DOI: 10.26355/eurrev_202311_34299 -
Biomedicine & Pharmacotherapy =... Dec 2023Psoriasis is a chronic inflammatory skin disease characterized by thickening the epidermis with erythema, scaling, and proliferation. Noscapine (NOS) has several...
Preparation and characterization of solid lipid nanoparticles encapsulated noscapine and evaluation of its protective effects against imiquimod-induced psoriasis-like skin lesions.
Psoriasis is a chronic inflammatory skin disease characterized by thickening the epidermis with erythema, scaling, and proliferation. Noscapine (NOS) has several anti-inflammatory, anti-angiogenic, and anti-fibrotic effects, but its low solubility and large size results in its lower efficacy in the clinic. In this regard, solid lipid nanoparticles (SLN) encapsulated NOS (SLN-NOS) were fabricated using the well-known response surface method based on the central composite design and modified high-shear homogenization and ultrasound method. As a result, Precirol® was selected as the best lipid base for the SLN formulation based on Hildebrand-Hansen solubility parameters, in which SLN-NOS 1 % had the best zeta potential (-35.74 ± 2.59 mV), average particle size (245.66 ± 17 nm), polydispersity index (PDI, 0.226 ± 0.09), high entrapment efficiency (89.77 %), and ICH-based stability results. After 72 h, the SLN-NOS 1 % released 83.23 % and 58.49 % of the NOS at pH 5.8 and 7.4, respectively. Moreover, Franz diffusion cell's results indicated that the skin levels of NOS for SLN and cream formulations were 46.88 % and 13.5 % of the total amount, respectively. Our pharmacological assessments revealed that treatment with SLN-NOS 1 % significantly attenuated clinical parameters, namely ear thickness, length, and psoriasis area and severity index, compared to the IMQ group. Interestingly, SLN-NOS 1 % reduced the levels of interleukin (IL)-17, tumor necrosis factor-α, and transforming growth factor-β, while elevating IL-10, compared to the IMQ group. Histology studies also showed that topical application of SLN-NOS 1 % significantly decreased parakeratosis, hyperkeratosis, acanthosis, and inflammation compared to the IMQ group. Taken together, SLN-NOS 1 % showed a high potential to attenuate skin inflammation.
Topics: Humans; Imiquimod; Noscapine; Lipids; Skin; Psoriasis; Nanoparticles; Inflammation
PubMed: 37924792
DOI: 10.1016/j.biopha.2023.115823 -
BMJ Case Reports Apr 2024A man in his 60s presented with a widespread erythematous rash and associated chills, paraesthesia and haematuria. He had recently commenced naproxen/esomeprazole. Blood...
A man in his 60s presented with a widespread erythematous rash and associated chills, paraesthesia and haematuria. He had recently commenced naproxen/esomeprazole. Blood tests showed hypereosinophilia (0.73×10/L) and moderate acute kidney injury. Histology revealed parakeratosis, mild spongiosis with eosinophils. He developed acute coronary syndrome with rapid atrial fibrillation. Coronary angiogram was non-obstructive. Cardiac MRI (CMR) revealed acute myocarditis secondary to Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Naproxen/esomeprazole was discontinued, and he was supported with oral corticosteroids. A repeat CMR 3 months later showed resolution of myocarditis. Naproxen/esomeprazole is not a common offending drug. DRESS is a rare drug-induced hypersensitivity reaction with a mortality rate of 10%. The objective of this case report is to highlight the significant but rare cardiac complications that can ensue from DRESS, which warrant prompt recognition and withdrawal of the causative drug.
Topics: Humans; Male; Drug Hypersensitivity Syndrome; Eosinophilia; Esomeprazole; Myocarditis; Naproxen; Middle Aged
PubMed: 38594198
DOI: 10.1136/bcr-2023-258187 -
BMJ Case Reports Jun 2024
Topics: Humans; Axilla; Parakeratosis; Female; Male
PubMed: 38862187
DOI: 10.1136/bcr-2023-257394 -
Journal of Advanced Research Dec 2023Rumen epithelial parakeratosis, a common disease in ruminants caused by abnormalities in the ruminal stratified squamous epithelial keratinization process, negatively...
INTRODUCTION
Rumen epithelial parakeratosis, a common disease in ruminants caused by abnormalities in the ruminal stratified squamous epithelial keratinization process, negatively impacts ruminant health and performance. However, we still lack a comprehensive perception of the underlying mechanisms and the predisposing factors for this disorder.
OBJECTIVES
Here, we investigated rumen epithelial cell heterogeneity, differentiation trajectories, and cornification to clarify the rumen epithelial keratinization process and discern the key ruminal metabolites contributing to rumen epithelial parakeratosis.
METHODS
Twenty-four 14-day-old lambs were divided into three groups, including only milk feeding, milk plus alfalfa hay feeding, and milk plus corn-soybean concentrate starter feeding. At 42 days of age, the lambs were slaughtered, and rumen tissues were collected for single-cell RNA-sequencing (scRNA-seq), immunofluorescence, and quantitative real-time PCR (qRT-PCR) analyses. Ruminal fluid samples were collected for metabolomic analyses. Rumen epithelial organoid was used to verify the key ruminal metabolites contributing to parakeratosis.
RESULTS
As expected, we observed that concentrate starter introduction resulted in rumen epithelial parakeratosis. Moreover, scRNA-seq analysis revealed a developmental impediment in the transition from differentiated keratinocytes to terminally differentiated keratinocytes (TDK) in lambs with concentrate starter introduction. Immunofluorescence and qRT-PCR analyses further verified the location and expression of marker genes of TDK. Metabolomic analysis showed a robust positive correlation between ruminal butyrate levels and rumen epithelial keratinization. More importantly, we successfully established a rumen organoid model capable of facilitating the study of the keratinization process in the rumen epithelia and further confirmed that high dose butyrate indeed contributed to rumen epithelial parakeratosis.
CONCLUSION
Collectively, concentrate starter introduction induces ruminal epithelial parakeratosis by blocking keratinocyte differentiation with excessive ruminal butyrate accumulation in a neonatal lamb model. These findings enhance our understanding of rumen epithelial keratinization and provide valuable insights for addressing rumen epithelial parakeratosis using early nutritional intervention strategies.
PubMed: 38128723
DOI: 10.1016/j.jare.2023.12.016 -
Head and Neck Pathology Jun 2024Uremic stomatitis is often unfamiliar to healthcare professionals. This study presents five cases of uremic stomatitis, providing a comprehensive analysis of their... (Review)
Review
BACKGROUND
Uremic stomatitis is often unfamiliar to healthcare professionals. This study presents five cases of uremic stomatitis, providing a comprehensive analysis of their demographic distribution, clinicopathological features, and management strategies based on existing literature.
METHODS
Data were collected from centers across Brazil, Argentina, Venezuela, and Mexico. Electronic searches were conducted in five databases supplemented by manual scrutiny and gray literature.
RESULTS
The series consisted of three men and two women with a mean age of 40.2 years. Lesions mostly appeared as white plaques, particularly on the tongue (100%). The median blood urea level was 129 mg/dL. Histopathological analysis revealed epithelial changes, including acanthosis and parakeratosis, with ballooned keratinocytes in the suprabasal region. Oral lesions resolved subsequent to hemodialysis in three cases (75%). Thirty-seven studies comprising 52 cases of uremic stomatitis have been described hitherto. Most patients were male (65.4%) with a mean age of 43.6 years. Clinically, grayish-white plaques (37.3%) and ulcers/ulcerations (28.9%) were common, particularly on the tongue (30.9%). Hemodialysis was performed on 27 individuals. The resolution rate of oral lesions was 53.3%.
CONCLUSION
Earlier recognition of uremic stomatitis, possibly associated with long-term uremia, holds the potential to improve outcomes for patients with undiagnosed chronic kidney disease.
Topics: Humans; Male; Female; Adult; Uremia; Stomatitis; Middle Aged; Latin America; Renal Dialysis
PubMed: 38896178
DOI: 10.1007/s12105-024-01652-3 -
International Journal of Surgical... Feb 2024Duchenne muscular dystrophy (DMD) is characterized by progressive systemic muscle wasting, leading to respiratory paralysis and early death. This X-linked disease is...
Duchenne muscular dystrophy (DMD) is characterized by progressive systemic muscle wasting, leading to respiratory paralysis and early death. This X-linked disease is caused by mutations, encoding dystrophin. There is little information regarding gastrointestinal abnormalities in patients with DMD. However, since the esophageal wall includes smooth and skeletal muscle it is also vulnerable to suffering the effects of muscle wasting in patients with DMD. After finding dyskeratosis and parakeratosis restricted to the proximal and middle esophagus with distal sparing in an 18-year-old patient with DMD, we performed an archive search of a large academic hospital and identified four additional patients with DMD who had also undergone esophageal biopsy. The patients consisted of five boys, ranging from 7 to 19 years of age. Esophageal injury was present in two patients, consisting of mild esophagitis in one, and spongiosis with dyskeratosis and parakeratosis in another. These patients were both older and had been diagnosed with DMD for greater than 15 years, while the three patients with histologically normal biopsies were younger and been diagnosed with DMD for 7, 9, and 13 years, respectively. Although the data is limited and the changes are subtle, they can be explained by the underlying muscular dystrophy pathophysiology.
Topics: Adolescent; Humans; Male; Esophagus; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Mutation; Parakeratosis; Child; Young Adult
PubMed: 37063046
DOI: 10.1177/10668969231167532 -
Clinical, Cosmetic and Investigational... 2023Granular parakeratosis (GP) is a unique keratotic disorder that often affects the intertriginous areas. GP usually presents as erythematous or brownish hyperkeratotic...
Granular parakeratosis (GP) is a unique keratotic disorder that often affects the intertriginous areas. GP usually presents as erythematous or brownish hyperkeratotic papules or plaques and can be further classified into five types. GP of the eccrine ostium is a rare subtype; its pathological defects are mainly localized to the stratum corneum of the eccrine ostia. Due to its rarity, there is usually a delay in diagnosing GP, and these patients are often misdiagnosed with other dermatological conditions. In this report, we present the case of a 64-year-old Thai female who presented with recurrent pruritic erythematous rashes on her neck since approximately 40 years. She was previously diagnosed with eczema or folliculitis. Histopathological examination confirmed a final diagnosis of GP of the eccrine ostium. She was advised to avoid excessive heat and keep her intertriginous areas dry. Her condition improved significantly during the follow-up visit.
PubMed: 37469551
DOI: 10.2147/CCID.S421152