Expression of Early Growth Response 3 in Skin Cancers.

OBJECTIVE: To assess the expression of early growth response 3 (EGR3) in normal skin and different types of skin tumors: cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), melanoma (MM), and cutaneous adnexal tumors containing sebaceous carcinoma (SC), trichoepithelioma (TE) and clear cell hidradenoma (CCH). BACKGROUND: EGR3, expressed in multiple organs, including skin, plays an important role in cell differentiation and tumor growth. Previous studies have shown that EGR3 suppresses tumor growth and is downregulated in various malignancies. However, its distribution in normal skin and its expression especially in skin tumors have not been studied. MATERIALS AND METHODS: Samples of normal cases (n = 4), cSCC (n = 12), BCC (n = 12), MM (n = 12), SC (n = 4), TE (n = 4), and CCH (n = 4) were collected from patients treated in our department between 2018 and 2023. Immunohistochemistry was used to investigate the expression of EGR3. The results were analyzed with the description of the staining pattern and the histochemical score. RESULTS: Immunohistochemical staining showed that EGR3 was uniquely expressed in normal skin in the granular layer and upper part of the stratum spinosum, as well as in sebaceous glands and hair follicles, but not in sweat glands. In skin cancers, BCC, SC, and TE showed positive EGR3 staining, whereas cSCC, MM, and CCH were negative. CONCLUSIONS: EGR3 has a specific expression pattern in normal skin and in skin tumors, which is important for the differential diagnosis of skin tumors, in particular for cSCC and sebaceous gland carcinoma.

Kimura's disease treated with dupilumab: A case report and literature review.

BACKGROUND: Kimura's disease (KD) is a rare chronic inflammatory disorder characterised by painless, deep subcutaneous nodules that most commonly affect the head and neck region of Asian men. Due to high relapse rates and side effects of current therapies, the treatment of KD is challenging. OBJECTIVES: To present a case of KD that was successfully treated with dupilumab and to review the literature with a focus on the evaluation of the efficacy and safety of dupilumab in KD. METHODS: A review of the available literature on the treatment of KD with dupilumab was performed and a new case was analyzed. To gain further insight into this promising therapy, literature review of 8 articles published between January 2016 and January 2024 were included in this study using the PubMed database. RESULTS: Our patient with KD was successfully treated with dupilumab 300 mg every 2 weeks, at an initial dose of 600 mg. The treatment was well tolerated. In the past, only nine patients with KD treated with dupilumab have been reported and reviewed, half of whom had failed prior treatment. All patients achieved significant efficacy after treatment with dupilumab, with no relapses during an average follow-up of 10.4 months (ranged from 4 to 16 months). CONCLUSION: Dupilumab may be an emerging alternative treatment option for KD patients. Larger randomized controlled studies are needed to confirm these findings.

Atypical plaque psoriasis: a clinicopathological study of 20 cases.

BACKGROUND: Plaque psoriasis is relatively straightforward to identify. When diagnostic concerns arise in atypical cases, a biopsy is needed. It is widely accepted that the Munro microabscess and the spongiform pustule of Kogoj are diagnostic pathological features. However, the diagnostic dilemma is likely to arise in cases without these specific pathological changes and typical clinical features. This study aimed to investigate clinical and pathological clues in distinguishing atypical plaque psoriasis from its mimics. METHODS: We evaluated the clinicopathological features of 20 cases of atypical plaque psoriasis and 40 cases of psoriasis mimics as controls including pityriasis rosea (n = 10), pityriasis lichenoides chronica (n = 8), and subacute dermatitis (n = 22). RESULTS: A retrospective analysis of the clinicopathological characteristics of patients with atypical plaque psoriasis and controls was performed. Pathologically, there were significant differences between the two groups in the types of parakeratosis (P = 0.046), epidermal capture of extravasated erythrocytes (P = 0.011), focal basal liquefied degeneration (P = 0.017), types of inflammatory cells (P = 0.000), and depth of inflammation (P = 0.000). Clinically, we found the presence of scales and crusts was significantly different between the two groups. CONCLUSION: This study offers insight into the clinicopathological features of atypical plaque psoriasis. These differential diagnostic features, compared with its mimics, are proposed to assist the clinician in the diagnosis and treatment of atypical plaque psoriasis.

HSP105 suppresses the progression of cutaneous squamous cell carcinoma by activating the P53 signaling pathway.

Cutaneous squamous cell carcinoma (cSCC) is a common type of nonmelanoma skin cancer with a very high incidence. Heat shock proteins (HSPs) are involved in abnormal proliferation, invasion and apoptosis of tumor cells. Whether HSP105 acts as a promoter or inhibitor of cSCC remains to be further explored. This study investigated the biological role of HSP105 in the progression of cSCC. Real-time PCR and Western blotting were used to detect the mRNA and protein expression of HSP105 in cSCC cell lines. Cell lines with overexpression and knockdown of HSP105 were established to analyze their cell cycle distribution, proliferation, apoptosis, migration, invasion and biological mechanisms. Finally, the proliferative effect of HSP105 in cSCC cells was verified in nude mice. We found that HSP105 expression was decreased in cSCC cell lines. Overexpression of HSP105 in A431 and SCL-1 cell lines induced cell cycle arrest and apoptosis, inhibited cell proliferation, reduced cell migration and invasion, and inhibited tumor growth in vivo. The opposite result was observed in the HSP105-silenced cell lines. Furthermore, HSP105 activated the P53 signaling pathway and exerted anticancer effects. Our findings provide new perspectives on the critical role and potential mechanisms of HSP105 in the development of cSCC, suggesting that HSP105 may be a novel therapeutic target for cSCC.

Effects of Gentiana delavayi Flower Extract on APP Processing in APP/PS1 CHO Cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana delavayi Franch. (Gentianaceae) as an ethnomedicinal plant contains a variety of effective active ingredients and exhibits diverse pharmacological actions, such as hepatoprotective, anti-inflammatory and central nervous system effects. In this study we investigated the influence of G. delavayi flower extract on amyloid precursor protein (APP) processing at molecular and cellular levels. APP/PS1 Chinese hamster ovary (CHO) cells were treated with chloroform extract of G. delavayi flower in different concentrations for 24 h. Concentrations of amyloid ß (Aß) 40 and Aß42 in the cell supernatant and activity of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1), BACE2, and cathepsin D were determined. The expression of APP and neprilysin (NEP) within the cell were further determined. Compared with the control group, the levels of Aß40 and Aß42 declined notably and the activity of BACE1 was inhibited significantly in the APP/PS1 CHO cells after treatment with the chloroform extract of G. delavayi flower. Although the activities of BACE2 and cathepsin D were not changed, the expression of Aß degrading enzyme NEP increased remarkably. Our experiments have clearly showed that the chloroform extract of G. delavayi flower inhibits the generation of ß-amyloid by specifically inhibiting ß-secretase and increases the expression of NEP which fastens the degradation of Aß, exhibiting the effect of decreasing Aß accumulation in APP/PS1 CHO cells. These results suggest that the active components from the chloroform extract of G. delavayi flower have a further prospect to be developed as potential anti-Aß drug.

N-stearoyl-l-Tyrosine inhibits the cell senescence and apoptosis induced by H2O2 in HEK293/Tau cells via the CB2 receptor.

Although considerable energy and money have been spent trying to inhibit Aß production and its related metabolic enzyme activities, there are still no drug treatments available to cure even slow for Alzheimer's disease. Therefore, tau protein has been focused recently as the new target for the treatment of Alzheimer's disease. The transfected human embryonic kidney 293 (HEK 293) cells with or without Tau 411 plasmid were used to evaluate the effect of tau protein on cell viability. H2O2 was added to simulate microenvironment of oxidative stress (OS) during aging. N-stearoyl-l-tyrosine (Nstyr), one of the synthesized N-arachidonoylethanolamide analogues was administrated in HEK293/Tau cells during H2O2 insults. Cellular senescence and tau aberrant modification appeared after tau transfection and aggravated by H2O2 insult which detected by ß-galactosidase staining analysis and western blotting analysis. The level of expression of Bcl-2 and the result of FCAS analysis indicated the appearance of cellular apoptosis. The expression of prosenescence moleculars such as p16-Rb and P53 were induced by tau transfection in HEK293 cells. Both p16-Rb and p53 senescent molecules were inhibited by Nstyr. AM251 (1 µM; an antagonist of CB1 cannabinoid receptor) or AM630 (1 µM; an antagonist of CB2 cannabinoid receptor) was used to offset the anti-senescence effects afforded by NsTyr. The anti-senescence and anti-apoptosis effect of NsTyr was completely abolished by AM630. Meanwhile, transfection of siRNACB2 was used to further confirm the above experimental results and it came out the similar results compared with AM630. Taken together, our results suggest that oxidative stress aggravates cellular senescence and apoptosis in HEK293/Tau, which can be reversed by Nstyr via CB2 receptor.

EIA application in China's expressway infrastructure: clarifying the decision-making hierarchy.

China's EIA Law came into effect in 2003 and formally requires road transport infrastructure development actions to be subject to Environmental Impact Assessment (EIA). EIAs (including project EIA and plan EIA, or strategic environmental impact assessment, SEA) have been being widely applied in the expressway infrastructure planning field. Among those applications, SEA is applied to provincial level expressway network (PLEI) plans, and project EIA is applied to expressway infrastructure development 'projects' under PLEI plans. Three case studies (one expressway project EIA and two PLEI plan SEAs) were examined to understand currently how EIAs are applied to expressway infrastructure development planning. Through the studies, a number of problems that significantly influence the quality of EIA application in the field were identified. The reasons causing those problems are analyzed and possible solutions are suggested aimed at enhancing EIA practice, helping deliver better decision-making and ultimately improving the environmental performance of expressway infrastructure.