Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Tuesday, May 4, 2021

Expression of HLA class I and class II genes in patients with multiple skin warts

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Abstract

Background

Human leukocyte antigens (HLAs), which are genetic markers that have critical roles in the immune response against pathogens, vary greatly among individuals.

Objectives

To investigate the frequency of HLA class I (HLA‐A, HLA‐B, and HLAC) and class II (HLA‐DRB1, HLA‐DQB1, and HLA‐DQA1) genes in patients with multiple skin warts and to elucidate the role of these genes in the genetic susceptibility to skin warts.

Methods

Peripheral venous blood samples were collected from 100 patients with multiple skin warts and 300 healthy individuals (controls). HLA typing was performed after DNA isolation from the blood samples.

Results

The HLA‐A*02 (odds ratio (OR): 0.12; p = 0.002), HLA‐DQA1*03:01 (OR: 0.45; p = 0.002), and DQA1*05:01 (OR: 0.17; p < 0.001) genes were significantly more prevalent in the patients than in the healthy individuals and were thus identified as risk genes. The DQA1*01:01 (OR: 0.17; p < 0.001), DQA1*01:02 (OR: 0.17; p < 0.001), and DQA1*01:03 (OR: 0.11; p < 0.001) genes were classified as protective genes because of their low frequencies in the patients.

Study limitation

Human papillomavirus typing could not be performed while investigating the relationship between skin warts and HLA class I and class II genes.

Conclusion

Our data suggest the role of HLA genes in the development of skin warts. However, other components of the major histocompatibility complex system and acquired factors of the immune system could also be involved and should be further investigated.

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A high‐throughput screening platform for pigment regulating agents using pluripotent stem cell‐derived melanocytes

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Abstract

In this study, we describe a simple and straightforward assay using induced pluripotent stem cell‐derived melanocytes and high‐throughput flow cytometry, to identify the effect induced by pigment regulating agents on melanin content. The assay is based on the correlation between forward light‐scatter characteristics and melanin content, with pigmented cells displaying high light absorption/low forward light scatter, while the opposite is true for lowly pigmented melanocytes, as a result of genetic background or chemical treatments. Orthogonal validation is then performed by regular melanin quantification. Such approach was validated using a set of 80 small molecules and yielded a confirmed hit. The assay described in this study may prove a useful tool to identify modulators of melanogenesis in human melanocytes.

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High‐frequency ultrasound as a scientific tool for skin imaging analysis

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Abstract

Ultrasonic imaging is one of the most important diagnostic tools in clinical medicine due to its cost, availability, and good correlation with pathological results. High‐frequency ultrasound (HFUS) is a technique used in skin science that has been little explored, especially in comparison to other sites and imaging techniques. HFUS shows real‐time images of the skin layers, appendages, and skin lesions in vivo, and can significantly contribute to advances in skin science. This review summarizes the potential applications of HFUS in dermatology and cosmetology, with a focus on quantitative tools that can be used to assess various skin conditions. Our findings showed that HFUS imaging is a reproducible and powerful tool for the diagnosis, clinical management, and therapy monitoring of skin conditions. It is also a helpful tool for assessing the performance of dermatological products. This technique may eventually become essential for evaluating the performance of dermatological and cosmetic products.

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Senescent cell removal via JAG1‐NOTCH1 signalling in the epidermis

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Abstract

Emerging evidence has pointed to the noxious effects of senescent cells in various tissues, and senescent cells in the epidermis are known to accumulate with age. We hypothesized that there is a mechanism by which senescent cells in the epidermis are preferentially removed and that the function of such removal mechanism declines as age increases. In this study, we investigated whether Notch signalling is involved in such senescent cell removal. We found that Notch1 receptor was expressed more highly in p16INK4a‐positive senescent cells than in surrounding cells in human epidermis both in young and old subjects. On the other hand, the expression of its ligand JAG1 was decreased in the epidermis of aged subjects. When normal epidermal cells and UVB‐irradiated senescent cells were mixed and three‐dimensional reconstructed epidermis was developed in vitro, the senescent cells were preferentially removed from the basal layer and located in the upper layer. We also found that the depletion of senescent cells from the basal layer was suppressed by JAG1 knockdown in normal cells or using a Notch signalling inhibitor. From these results, Notch signalling may be involved in senescent cell removal in the epidermis and the age‐related decrease of JAG1 expression in the basal layer may lead to accumulation of senescent cells owing to reduced activation of Notch signalling.

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Intraventricular meningioma admixed with choroid plexus papilloma: a rare case report with review of literature

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Int J Clin Exp Pathol. 2021 Apr 15;14(4):545-550. eCollection 2021.

ABSTRACT

A 42-year-old male presented with a history of headaches for the previous 2 weeks. Magnetic resonance imaging of the brain showed a 3 cm-sized well-defined, enhancing mass in the atrium of the right lateral ventricle. The tumor comprised two heterogeneous components: approximately one-third of the tumor exhibited complex and delicate papillary fibrovascular cores lined with uniform cuboidal-to-columnar epithelial cells, whereas the remaining part was seen as a solid sheet comprising ovoid-to-spindle cells with plump cytoplasm, which occasionally had a whorling pattern. Further, immunohistochemical staining with cytokeratin 7 (CK7) and epithelial membrane antigen (EMA) clearly demarcated each component: the CK7+/EMA- choroid plexus papilloma and CK7-/EMA+ meningioma. This report provides a description of an unusual case of concomitant choroid plexus papilloma a nd ventricular meningioma presenting as a single mass, along with a review of relevant literature.

PMID:33936380 | PMC:PMC8085822

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Application of metagenomic next-generation sequencing (mNGS) combined with rapid on-site cytological evaluation (ROSCE) for the diagnosis of Chlamydia psittaci pneumonia

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Int J Clin Exp Pathol. 2021 Apr 15;14(4):389-398. eCollection 2021.

ABSTRACT

We evaluated the application of metagenomic next-generation sequencing (mNGS) combined with rapid on-site cytological evaluation (ROSCE) in the diagnosis of Chlamydia psittaci pneumonia, to provide a basis for an accurate diagnosis. Clinical data from three patients with C. psittaci pneumonia diagnosed by the combination of mNGS and ROSCE from June 2019 to June 2020 in the Department of Respiratory and Critical Care Medicine of Tianjin Medical University General Hospital were reviewed. Three patients with community-acquired pneumonia failed to respond to the initial treatment, and were finally diagnosed by bronchoscopic lung biopsy and alveolar lavage fluid (BALF) mNGS. According to the ROSCE cytologic characteristics, the scope of the lesions was narrowed to inflammatory lesions excluding tumor and other non-infectious lesions. Subsequently, mNG S results confirmed that the three patients were infected by C. psittaci, sequence numbers 2066, 126, and 1077, respectively. Two patients developed severe pneumonia and required organ function support. The other patient had recurrent high fever and severe headache, which significantly complicated clinical diagnosis and treatment. Eventually, the treatment plan was adjusted according to the mNGS results, resulting in gradual improvement of symptoms and satisfactory prognosis. mNGS combined with ROSCE is effective for the accurate diagnosis and treatment of C. psittaci pneumonia, having significant advantages in comparison with other detection methods, particularly in the cases of rare pathogens, mixed pathogen infections, and immunodeficient patients.

PMID:33936360 | PMC:PMC8085828

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Resiniferatoxin reduces cardiac sympathetic nerve activation to exert a cardioprotective effect during myocardial infarction

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Int J Clin Exp Pathol. 2021 Apr 15;14(4):408-416. eCollection 2021.

ABSTRACT

BACKGROUND AND OBJECTIVE: Myocardial infarction (MI) is a common critical disease of the cardiovascular system. The process of MI is often accompanied by the excessive activation of cardiac sympathetic nerves, which leads to arrhythmia. Resiniferatoxin (RTX) is a transient receptor potential vanilloid 1 (TRPV1), involved in the cardiac sympathetic afferent reflex. However, whether RTX can reduce the occurrence of arrhythmia and exert a cardioprotective effect by inhibiting the sympathetic reflex during MI is still unknown.

METHODS: The left anterior descending artery of cardiac was clamped to construct a model of MI. RTX (50 μg/ml) was used by epicardial application in MI rats. Ventricular electrophysiologic properties were continuously monitored by a body surface ECG. Yrosine hydroxylase (TH) and growth associated protein 43 (GAP43) were detected by Im munofluorescence staining. Connexin43 and transforming growth factor beta receptor 1 (TGF-β1) were detected by western blot. Norepinephrine (NE) and BNP levels in blood and tissue were determined by ELISA. Cardiac function was assessed by echocardiography.

RESULTS: The ERP, APD90, QRS, QT and the Tend-Tpeak intervals in MI rats were all prolonged, but decreased after RTX treatment (n = 3, P<0.05). In contrast, the RR interval was shortened in the MI group, but prolonged in the MI+RTX group (n = 3, P<0.05). RTX treatment significantly reduced ventricular arrhythmias after MI. TH- and GAP43-positive nerve densities and TGF-β1, and cx-43 protein expression were up-regulated in the MI group compared to the sham group, and they were decreased in the MI+RTX group compared to the MI group (n = 3, P<0.05). RTX can decrease serum and tissue NE and BNP levels (n = 3, P<0.05). RTX pretreatment significantly decreased h eart rate, HW/BW ratio and LVIDS, and increased LVEF andLVFS values (n = 3, P<0.05).

CONCLUSION: RTX improved cardiac dysfunction, ventricular electrophysiologic properties, and sympathetic nerve remodeling in rats with MI by inhibiting the excessive cardiac sympathetic drive.

PMID:33936362 | PMC:PMC8085824

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IL-1β promotes cervical cancer through activating NF-κB/CCL-2

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Int J Clin Exp Pathol. 2021 Apr 15;14(4):426-433. eCollection 2021.

ABSTRACT

Cervical cancer is a malignancy with high morbidity and mortality among women. Interleukin (IL)-1β, chemokine (C-C motif) ligand 2 (CCL-2), and activation of NF-κB have been proven to be closely related to the progression of various tumors. However, their role in cervical cancer remains unclear. Cell proliferation, migration, and invasion were detected using MTT, wound healing, and transwell assays. Western blotting and qRT-PCR were used to measure expression of target genes. IL-1β greatly promoted the release of CCL-2 from HeLa cells. Activation of NF-κB and phosphorylated NF-κB (p65) nuclear translocation were accelerated by IL-1β. TPCA-1, a blocker of NF-κB, significantly inhibited the release of CCL-2 from HeLa cells. TPCA-1 markedly reversed the promotional effect of IL-1β on viability of HeLa cells. IL-1β increased the cell migration, proliferat ion, and invasion of HeLa cells through targeting the NF-κB/CCL-2 pathway. IL-1β/NF-κB/CCL-2 might be a promising treatment target for cervical cancer treatment and prevention.

PMID:33936364 | PMC:PMC8085834

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Solitary rectal ulcer syndrome in children and adolescents: a descriptive clinicopathologic study

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Int J Clin Exp Pathol. 2021 Apr 15;14(4):399-407. eCollection 2021.

ABSTRACT

Solitary rectal ulcer syndrome (SRUS) is an uncommon disorder of the rectum. While benign, it can cause concern for patients and affect quality of life. Reported studies on SRUS worldwide are scarce. The aim of this study is to describe the clinicopathologic characteristics of SRUS in a cohort of children based in Saudi Arabia. In this study, children with a confirmed diagnosis of SRUS at King Abdulaziz University Hospital (KAUH) were included, during the period November 2003 to November 2017. Data were collected from hospital medical records. The study comprised twenty-one patients: 17 males (81%) and 4 females (19%); the median age was 11.4 years (range, 5.43-17.9 years). The most common presenting symptoms were rectal bleeding in 21 patients (100%), passage of mucus in 16 (76.1%), abdominal pain in 14 (66.6%), constipation in 13 (61.9%), straining in 9 (42. 9%), and rectal prolapse in 5 (23.8%). The most common finding at initial colonoscopy was a single ulcer in 7 patients (33.3%), multiple ulcers in 6 (28.5%), polypoid lesions in 5 (23.8%), and hyperemic mucosa in 3 (14.2%). All patients received medical treatment and 14 (81%) continued to manifest one or more of the symptoms following treatment, which required subsequent modification of the treatment course. None of the patients required surgery. In conclusion, the study found rectal bleeding to be the most common presentation, with a single ulcer being the most prevalent lesion in endoscopy. Treatment response was variable, but almost half of patients reported relief of symptoms following treatment.

PMID:33936361 | PMC:PMC8085826

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Long non-coding RNA CYTOR regulates proliferation and metastasis of colon cancer cells through regulating miRNA-105/PTEN axis

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Int J Clin Exp Pathol. 2021 Apr 15;14(4):434-443. eCollection 2021.

ABSTRACT

Colon cancer is a common malignancy, and its incidence and mortality have been increasing in recent years. This study aims to explore the regulation of long non-coding RNA CYTOR on proliferation and metastasis of colon cancer cells through miRNA-105/PTEN axis. Real-time quantitative PCR (qRT-PCR) disclosed that expression of CYTOR was significantly decreased in colon cancer tissues, compared with that of adjacent normal tissues, while miRNA-105 was significantly increased. Correlation study found that CYTOR was negatively correlated with miR-105. The proliferation, migration, and invasion rates of the LoVo cells with highly expressed CYTOR were significantly slower. miR-105 mimic could suppress the decrease in proliferation, migration, and invasion rates of colon cancer cells caused by overexpression of CYTOR. Additionally, the proliferation, migration, and in vasion rates of the LoVo cells in miR-105 inhibition group were significantly slower. The Starbase database predicted the targeting of miR-105 by CYTOR, and qRT-PCR and dual luciferase reporter gene method were used to verify the targeting relationship of CYTOR and miRNA-105/PTEN axis. In conclusion, CYTOR can inhibit the proliferation and metastasis of colon cancer cells through targeted inhibition of the miR-105/PTEN axis.

PMID:33936365 | PMC:PMC 8085819

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Effect of resveratrol on abnormal bone remodeling and angiogenesis of subchondral bone in osteoarthritis

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Int J Clin Exp Pathol. 2021 Apr 15;14(4):417-425. eCollection 2021.

ABSTRACT

PURPOSE: The effect of resveratrol on subchondral bone in osteoarthritis was explored by constructing a mouse model of osteoarthritis and giving resveratrol as intervention.

METHODS: The degree of proteoglycan loss in articular cartilage was assessed by safranine fast green staining. The expressions of Lubricin and Aggrecan, COLX, and MMP-13, the co-expression of CD31 and Endomucin, and the expression of angiogenesis-related factors were determined by immunohistochemistry. TRAP stain and immunostaining were used to assess abnormal subchondral bone resorption and bone formation. Angiography was employed to analyze the effect of resveratrol on the proliferation of subchondral bone vessels.

RESULTS: Resveratrol inhibited cartilage thickening and the increase of COLX and MMP-13 expression, delayed the loss of proteoglycan, Lubricin, and Aggrecan, and i nhibited osteoclast differentiation by up-regulating osteoprotegerin (OPG) and down-regulating the expression of RANKL. Angiography showed that resveratrol can reduce the abnormally elevated number and volume of blood vessels in the subchondral bone. Immunostaining showed that resveratrol inhibited CD31hiEmcnhi angiogenesis and high expression of VEGFA and Angiopoietin-1.

CONCLUSION: Resveratrol inhibits osteoclast differentiation and reduces active bone resorption by regulating the OPG/RANKL/RANK pathway, and inhibits the abnormal proliferation of CD31hiEmcnhi blood vessels by downregulating the expression of VEGFA and Angiopoiein-1, thereby eliminating the pathologic coupling mechanism of osteogenesis and vascularization, and delaying the progression of osteoarthritis.

PMID:33936363 | PMC:PMC8085829

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