Notch

Tuberous sclerosis complex-associated renal cell carcinoma (TSC-RCC) has distinct clinical and histopathologic features and is considered a specific subtype of RCC. The genetic alterations of TSC1 or TSC2 are responsible for the development of TSC. In this study, we assessed the mTOR pathway activation and aimed to evaluate molecular characteristics and pathogenic pathways of TSC-RCC. Two cases of TSC-RCC, one from a 31-year-old female and the other from an 8-year-old male, were assessed. The mTOR pathway activation was determined by immunohistochemistry...

The IRF8-dependent subset of classical dendritic cells (cDCs), termed cDC1, is important for cross-priming cytotoxic T cell responses against pathogens and tumors. Culture of hematopoietic progenitors with DC growth factor FLT3 ligand (FLT3L) yields very few cDC1s (in humans) or only immature "cDC1-like" cells (in the mouse). We report that OP9 stromal cells expressing the Notch ligand Delta-like 1 (OP9-DL1) optimize FLT3L-driven development of cDC1s from murine immortalized progenitors and primary bone marrow cells...

BACKGROUND: Orofacial clefts include cleft lip only (CLO), cleft palate only (CPO), and cleft lip with palate (CLP). Previously, we reported the expression profile of plasma microRNAs in CLO, CPO, and CLP, respectively. However, the interaction of each subtype remains poorly investigated. METHODS: In this study, we integrated the expression profiles of plasma miRNAs in these 3 subtypes, and assessed the distinct and overlapping dysregulated miRNAs using Venn diagrams...

Epidermal growth factor-like domain-containing protein 7 (EGFL7), a member of the epidermal growth factor (EGF)-like protein family, is a potent angiogenic factor expressed in many different cell types. EGFL7 plays a vital role in controlling vascular angiogenesis during embryogenesis, organogenesis, and maintaining skeletal homeostasis. It regulates cellular functions by mediating the main signaling pathways (Notch, integrin) and EGF receptor cascades. Accumulating evidence suggests that Egfl7 plays a crucial role in cancer biology by modulating tumor angiogenesis, metastasis, and invasion...

Objectives: Osteoarthritis (OA), characterized by degradation of articular cartilage, is a leading cause of disability. As the only cell type present in cartilage, chondrocytes play curial roles in the progression of OA. In our study, we aimed to explore the roles of miR-23b in the lipopolysaccharide (LPS)-induced inflammatory injury. Materials and Methods: LPS-induced cell injury of ATDC5 cells was evaluated by the loss of cell viability, enhancement of cell apoptosis, alteration of apoptosis-associated proteins, and release of inflammatory cytokines...

Background: Doxorubicin is a widely used chemotherapy drug for the treatment of a variety of cancers, however it also has serious side effects such as anaphylaxis and heart damage. Therefore, it's very important to understand the downstream molecular pathways that are essential for Doxorubicin function in cancer treatment. Methods: HeLa S3 cells were treated with different concentrations of Doxorubicin for 24 hours. Then, the mRNA levels of Notch pathway components in the Doxorubicin treated cells were determined by Real-Time qRT-PCR...

The majority of cervical cancer (CC) cases are attributable to HPV infection. Altered Notch pathway signals and HPV are believed to modify clinicopathogenesis of CC, however, the involvement of each molecular player and its mechanism is still not known. Jagged-1 (JAG1) is one of the ligands that induce Notch pathway. The involvement of JAG1 in the modulation of a disease condition is not very clear. Hence, this study aims to study the role of JAG1 in HPV-16/18 associated different histological sub-types of CC, especially ADC...

Objective: To explore the effect of individualized multi-compound sound therapy on chronic subjective tinnitus and the relationship between tinnitus frequency," notch " hearing loss and the treatment effect of sound therapy. Method: Seventy-eight cases of chronic subjective tinnitus with the pure tone test threshold (PTA)in normal range (≤25 dB HL)were enrolled in this study. Their hearing threshold were re-evaluated using the precise pure-tone audiogram (P-PTA).Tinnitus was evaluated on pitch and loudness matching, and the effectiveness of tinnitus was measured using Tinnitus Handicap Inventory (THI) before they received the individualized customized multi-compound sound therapy for 3 months...

OBJECTIVE: Gastric cancer is the most common gastrointestinal malignancy and the leading cause of cancer-related deaths in East Asia. Increasing evidence has revealed that autophagy is closely associated with tumor initiation and progression. The present work aimed to investigate the role of autophagy in adjuvant chemotherapy for gastric cancer. MATERIALS AND METHODS: Gastric cancer stem cells (CSCs) were isolated from gastric cancer cell lines using the cell surface markers CD44 and CD54 and cultured in a three-dimensional cell culture system...

Background and Aims: Disturbance of intestinal homeostasis is associated with the development of inflammatory bowel disease (IBD), and TGF-β signaling impairment in mononuclear phagocytes (MPs) causes murine colitis with goblet cell depletion. Here, we examined an organoid-MP co-culture system to study the role of MPs in intestinal epithelial differentiation and homeostasis. Methods: Intestinal organoids were co-cultured with lamina propria leukocytes and bone marrow-derived dendritic cells (BMDCs) from CD11c-cre Tgfbr2fl/fl mice...

Cancer immunotherapy, which stimulates or augments host immune responses to treat malignancies, is the latest development in the rapidly advancing field of cancer immunology. The basic principles of immunotherapies are either to enhance the functions of specific components of the immune system or to neutralize immune-suppressive signals produced by cancer cells or tumor microenvironment cells. When successful, these approaches translate into long-term survival for patients. However, durable responses are only seen in a subset of patients and so far, only in some cancer types...

Presenilin-1 (PSEN1) is the catalytic subunit of the γ-secretase complex, and pathogenic mutations in the PSEN1 gene account for the majority cases of familial AD (FAD). FAD-associated mutant PSEN1 proteins have been shown to affect APP processing and Aβ generation and inhibit Notch1 cleavage and Notch signaling. In this report, we found that a PSEN1 mutation (S169del) altered APP processing and Aβ generation, and promoted neuritic plaque formation as well as learning and memory deficits in AD model mice...

Radiation exposure severely damages the hematopoietic system. Although several radio-protectors have been proposed to prevent radiation-induced damage, most agents have limited efficacy. In the present study, we investigated whether mesenchymal stem cells (MSCs) could contribute to the expansion of hematopoietic cells and mitigate radiation-induced hematopoietic injury in vitro and in vivo. We found that co-culture with MSCs promoted hematopoietic progenitor/stem cell (HPSCs) maintenance by providing a bone marrow-like microenvironment...

The lower gluteal flap is an autologous microsurgical breast reconstruction procedure using the soft tissue of the region of the gluteal sulcus. The perineal extension increases the volume of the sample. The pedicle with one artery and two large veins extends up the ischial notch and can reach 8 to 12cm. The two operative positions, the relative shortness of the pedicle and the firm tissues transferred are balanced by the discretion of the sequelae of the donor site and the volume which is always enough even in the slim woman...

Glycolysis, the classic pathway for producing energy, has been known to be involved in neural development. Notch signaling also contributes to neural development and regulation of glycolysis in various tissues. However, the role of Notch signaling in glycolysis-related gene regulation during neural development is poorly understood. Here, we analyzed mRNA expression patterns and levels of glucose transporters (GLUT) as well as rate-limiting enzymes in glycolysis using zebrafish mib1ta52b mutants, in which Notch signaling was deficient at the early embryonic and larval stages...

Heterotopic ossification and scapular notching are common following reverse total shoulder arthroplasty. Compared with the original Grammont-style prosthesis with a medialized center of rotation (COR) and a 155° neck-shaft angle, lateralization of COR and reduction of neck-shaft angle have been associated with decreased incidence of scapular notching. The authors hypothesized that these design features may also be effective in reducing heterotopic ossification after reverse total shoulder arthroplasty. Ninety-seven consecutive patients who underwent reverse total shoulder arthroplasty performed by a single surgeon were included in the study...

The Notch signaling pathway participates in several cellular functional aspects. This signaling has an important role in targeting both DC maturation and DC-mediated T cell responses. Thus, it is essential to investigate the influence of this signaling pathway in the role played by DCs in the pathogenesis of experimental paracoccidioidomycosis. This disease is a granulomatous and systemic mycosis that mainly affects lung tissue and can spread to any other organ and system. In this study, we demonstrated that bone marrow-derived DCs infected with yeasts from Paracoccidioides brasiliensis strain 18 performed efficiently their maturation after the activation of Notch signaling, with an increase in CD80, CD86, CCR7, and CD40 expression and the release of cytokines such as IL-6 and TNF-α...

The Notch receptor is an evolutionarily highly conserved transmembrane protein essential to a wide spectrum of cellular systems, and its deregulation has been linked to a vast number of developmental disorders and malignancies. Regulated Notch function is critical for the generation of T-cells, in which abnormal Notch signaling results in leukemia. Notch activation through trans -activation of the receptor by one of its ligands expressed on adjacent cells has been well defined. In this canonical ligand-dependent pathway, Notch receptor undergoes conformational changes upon ligand engagement, stimulated by a pulling-force on the extracellular fragment of Notch that results from endocytosis of the receptor-bound ligand into the ligand-expressing cell...

Background and Aims: The sniffing position has been most commonly used for positioning of the head and neck to facilitate tracheal intubation. However, the optimum degree of head elevation for the optimal laryngeal view is not well studied, especially in non-Western countries. The present study was aimed to compare the use of a fixed height pillow versus a customised pillow (CP) height for head elevation, in terms of glottis visualisation and time required for tracheal intubation. Methods: With research and ethics committee approval from the institute, this randomised study was conducted among patients of both sexes aged 16 years or more and American Society of Anesthesiologists physical Status I to IV...

INTRODUCTION: In the absence of any robust data supporting the TNM classification of T4 buccal mucosa cancers, we did this prospective study to compare the oncologic outcomes of T4a and T4b buccal mucosa cancer patients. PATIENTS AND METHODS: This is a prospective study of 210 treatment naïve T4 buccal mucosa cancer patients. All patients underwent upfront radical surgery followed by adjuvant radiotherapy (RT)/chemoradiotherapy (CCRT). This is the largest prospective series in the literature on T4 buccal cancers...