Immune Control by TRAF6-Mediated Pathways of Epithelial Cells in the EIME (Epithelial Immune Microenvironment)

In the protective responses of epithelial tissues, not only immune cells but also non-immune cells directly respond to external agents. Epithelial cells can be involved in the organization of immune responses through two phases. First, the exogenous harmful agents trigger the primary responses of the epithelial cells leading to various types of immune cell activation. Second, cytokines produced by the immune cells that are activated directly by the external agents and indirectly by the epithelial cell products elicit the secondary responses giving rise to further propagation of immune responses. TRAF6 is a ubiquitin E3 ligase, which intermediates between various types of receptors for exogenous agents or endogenous mediators and activation of subsequent transcriptional responses via NF-kappaB and MAPK pathways. TRAF6 ubiquitously participates in many protective responses in immune and non-immune cells. Particularly, epithelial TRAF6 has an essential role in the primary and secondary responses via driving type 17 response in psoriatic inflammation of the skin. Consistently, many psoriasis susceptibility genes encode the TRAF6 signaling players, such as ACT1 (TRAF3IP2), A20 (TNFAIP3), ABIN1 (TNIP1), IL-36Ra (IL36RN), IkappaBzeta (NFKBIZ), and CARD14. Herein, we describe the principal functions of TRAF6, especially in terms of positive and regulatory immune controls by interaction between immune cells and epithelial cells. In addition, we discuss how TRAF6 in the epithelial cells can organize the differentiation of immune responses and drive inflammatory loops in the epithelial immune microenvironment, which is termed EIME

Immune Control by TRAF6-Mediated Pathways of Epithelial Cells in the EIME (Epithelial Immune Microenvironment)

In the protective responses of epithelial tissues, not only immune cells but also non-immune cells directly respond to external agents. Epithelial cells can be involved in the organization of immune responses through two phases. First, the exogenous harmful agents trigger the primary responses of the epithelial cells leading to various types of immune cell activation. Second, cytokines produced by the immune cells that are activated directly by the external agents and indirectly by the epithelial cell products elicit the secondary responses giving rise to further propagation of immune responses. TRAF6 is a ubiquitin E3 ligase, which intermediates between various types of receptors for exogenous agents or endogenous mediators and activation of subsequent transcriptional responses via NF-kappaB and MAPK pathways. TRAF6 ubiquitously participates in many protective responses in immune and non-immune cells. Particularly, epithelial TRAF6 has an essential role in the primary and secondary responses via driving type 17 response in psoriatic inflammation of the skin. Consistently, many psoriasis susceptibility genes encode the TRAF6 signaling players, such as ACT1 (TRAF3IP2), A20 (TNFAIP3), ABIN1 (TNIP1), IL-36Ra (IL36RN), IkappaBzeta (NFKBIZ), and CARD14. Herein, we describe the principal functions of TRAF6, especially in terms of positive and regulatory immune controls by interaction between immune cells and epithelial cells. In addition, we discuss how TRAF6 in the epithelial cells can organize the differentiation of immune responses and drive inflammatory loops in the epithelial immune microenvironment, which is termed EIME

The association between smoking and risk of skin cancer: a meta-analysis of cohort studies

The association between smoking and the risk of skin cancers has been studied without reaching consistent findings. This study aims to assess this association through an updated meta-analysis of cohort studies.; We retrieved cohort studies that investigated the temporal association between smoking and the risk of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM). Pooled relative risks (RRs) and confidence intervals (CIs) of the included articles were calculated for current, former, and heavy smoking compared with never smoking. Publication bias was detected using the Egger's regression.; A total of 15 studies, published between 1990 and 2018, were included. Current smoking was associated with a higher risk of SCC (pooled RR = 1.32, 95% CI 1.15, 1.52) but with a lower risk of BCC (pooled RR = 0.85, 95% CI 0.75, 0.96) and MM (pooled RR = 0.72, 95% CI 0.64, 0.82). No publication bias was detected, and no single study had a substantial impact on the pooled results. Similar results were detected for heavy smoking, while former smoking was not associated with the risk of skin cancer.; Current smoking and heavy smoking were associated with a higher risk of SCC but a decreased risk of BCC and MM, while former smoking was not associated with skin cancer risk

A Novel Classification Model of Date Fruit Dataset Using Deep Transfer Learning

Date fruits are the most common fruit in the Middle East and North Africa. There are a wide variety of dates with different types, colors, shapes, tastes, and nutritional values. Classifying, identifying, and recognizing dates would play a crucial role in the agriculture, commercial, food, and health sectors. Nevertheless, there is no or limited work to collect a reliable dataset for many classes. In this paper, we collected the dataset of date fruits by picturing dates from primary environments: farms and shops (e.g., online or local markets). The combined dataset is unique due to the multiplicity of items. To our knowledge, no dataset contains the same number of classes from natural environments. The collected dataset has 27 classes with 3228 images. The experimental results presented are based on five stages. The first stage applied traditional machine learning algorithms for measuring the accuracy of features based on pixel intensity and color distribution. The second stage applied a deep transfer learning (TL) model to select the best model accuracy of date classification. In the third stage, the feature extraction part of the model was fine-tuned by applying different retrained points to select the best retraining point. In the fourth stage, the fully connected layer of the model was fine-tuned to achieve the best classification configurations of the model. In the fifth stage, regularization was applied to the classification layer of the best-selected model from the fourth stage, where the validation accuracy reached 97.21% and the best test accuracy was 95.21%

Prevalence and patterns of female sexual dysfunction among overweight and obese premenopausal women in Upper Egypt; a cross sectional study

Objective: Obesity is a growing public health concern. Many reports link obesity to female sexuality. The purpose of this study is to assess the prevalence and patterns of female sexual dysfunction (FSD) among overweight and obese premenopausal women in Beni-Suef, Egypt. Study design: A cross sectional study. Setting: Beni-Suef, Egypt. Subjects and methods: 150 premenopausal non-pregnant married women were enrolled for the study. Socio-demographic characteristics and obstetric history were collected using a self-administered questionnaire. Sexual dysfunction was assessed using the Arabic version of female sexual function index (ArFSFI). Results: The mean age of the participating women was 31.2 ± 7.3 years and the mean BMI was 27.5 ± 1.9 kg/m2. Circumcision was reported by 59.3% of women. Precisely, 42 (28%) of women had FSD. Pain, lubrication and arousal were the most common reported problems 69.3%, 53.3% and 52%, respectively. Obese women were more likely to have desire, arousal and lubrication problems compared to the overweight. FSFI total score correlated negatively with age of women, marriage duration and parity (p  0.05). Conclusion: Problems in pain, lubrication and arousal were the most common patterns of sexual dysfunction among overweight Egyptian women. Further research over the effect of certain interventional programs on FSD should be considered

Sleep pattern changes in patients with lung cancer

Background: There are multiple connections between sleep and lung cancer.  Both of them impacting each other  lung cancer can make it difficult to sleep well due to symptoms and treatment side effects( 20-70% of  cancer patients suffer of insomnia) .Also there is possible relationship between lung cancer and nocturnal intermittent hypoxia, apnea and daytime sleepiness,  progression of lung cancer  considered as risk factor of obstructive sleep apnea severity. Aim of the work: to evaluate sleep pattern changes in patients with lung cancer. Patients and methods: 26 patients with non small cell lung cancer  were  interviewed for assessment of histopathological subtypes and stages according to TNM classification and treated at Department of Clinical Oncology and Nuclear Medicine (chemotherapy, radiotherapy, targeted therapy and surgical treatment were scheduled), they underwent to sleep questionnaire and Epworth Sleepiness Score (ESS).overnight full polysomnography was done

Adrenomedullin Mitigates Doxorubicin-Induced Nephrotoxicity in Rats: Role of Oxidative Stress, Inflammation, Apoptosis, and Pyroptosis

Doxorubicin (DOX) is an anticancer antibiotic which has various effects in human cancers. It is one of the commonly known causes of drug-induced nephrotoxicity, which results in acute renal injury. Adrenomedullin (ADM), a vasodilator peptide, is widely distributed in many tissues and has potent protective effects. Therefore, the current study aimed to examine the protective potential mechanisms of ADM against DOX-induced nephrotoxicity. A total of 28 male Wistar rats were randomized into four groups: control group, doxorubicin group (15 mg/kg single intraperitoneal injection of DOX), adrenomedullin + doxorubicin group (12 μg/kg/day intraperitoneal injection of ADM) 3 days prior to DOX injection and continuing for 14 days after the model was established, and adrenomedullin group. Kidney function biomarkers, oxidative stress markers, and inflammatory mediators (TNF-α, NLRP3, IL-1β, and IL-18) were assessed. The expressions of gasdermin D and ASC were assessed by real-time PCR. Furthermore, the abundances of caspase-1 (p20), Bcl-2, and Bax immunoreactivity were evaluated. ADM administration improved the biochemical parameters of DOX-induced nephrotoxicity, significantly reduced oxidative damage markers and inflammatory mediators, and suppressed both apoptosis and pyroptosis. These results were confirmed by the histopathological findings and revealed that ADM’s antioxidant, anti-inflammatory, anti-apoptotic, and anti-pyroptotic properties may have prospective applications in the amelioration of DOX-induced nephrotoxicity

Clinical and genetic differences between pustular psoriasis subtypes

The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations. We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort. We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases. Psoriasis vulgaris concurrence was lowest in PPP (15.8% vs 54.4% in GPP and 46.2% in ACH, P <.0005 for both), whereas the mean age of onset was earliest in GPP (31.0 vs 43.7 years in PPP and 51.8 years in ACH, P <.0001 for both). The percentage of female patients was greater in PPP (77.0%) than in GPP (62.5%; P = 5.8 × 10 ). The same applied to the prevalence of smokers (79.8% vs 28.3%, P < 10 ). Although AP1S3 alleles had similar frequency (0.03-0.05) across disease subtypes, IL36RN mutations were less common in patients with PPP (0.03) than in those with GPP (0.19) and ACH (0.16; P = 1.9 × 10 and.002, respectively). Importantly, IL36RN disease alleles had a dose-dependent effect on age of onset in all forms of pustular psoriasis (P =.003). The analysis of an unparalleled resource revealed key clinical and genetic differences between patients with PPP and those with GPP

Clinical and genetic differences between pustular psoriasis subtypes

Background: The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations. Objective: We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort. Methods: We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases. Results: Psoriasis vulgaris concurrence was lowest in PPP (15.8% vs 54.4% in GPP and 46.2% in ACH, P &lt; .0005 for both), whereas the mean age of onset was earliest in GPP (31.0 vs 43.7 years in PPP and 51.8 years in ACH, P &lt; .0001 for both). The percentage of female patients was greater in PPP (77.0%) than in GPP (62.5%; P = 5.8 × 10−5). The same applied to the prevalence of smokers (79.8% vs 28.3%, P &lt; 10−15). Although AP1S3 alleles had similar frequency (0.03-0.05) across disease subtypes, IL36RN mutations were less common in patients with PPP (0.03) than in those with GPP (0.19) and ACH (0.16; P = 1.9 × 10−14 and .002, respectively). Importantly, IL36RN disease alleles had a dose-dependent effect on age of onset in all forms of pustular psoriasis (P = .003). Conclusions: The analysis of an unparalleled resource revealed key clinical and genetic differences between patients with PPP and those with GPP