Hippo-YAP/TAZ signaling in breast cancer: Reciprocal regulation of microRNAs and implications in precision medicine

Breast cancer is a molecularly heterogeneous disease and the most common female malignancy. In recent years, therapy approaches have evolved to accommodate molecular diversity, with a focus on more biologically based therapies to minimize negative consequences. To regulate cell fate in human breast cells, the Hippo signaling pathway has been associated with the alpha subtype of estrogen receptors. This pathway regulates tissue size, regeneration, and healing, as well as the survival of tissue-specific stem cells, proliferation, and apoptosis in a variety of organs, allowing for cell differentiation. Hippo signaling is mediated by the kinases MST1, MST2, LATS1, and LATS2, as well as the adaptor proteins SAV1 and MOB. These kinases phosphorylate the downstream effectors of the Hippo pathway, yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ), suppressing the expression of their downstream target genes. The Hippo signaling pathway kinase cascade plays a significant role in all cancers. Understanding the principles of this kinase cascade would prevent the occurrence of breast cancer. In recent years, small noncoding RNAs, or microRNAs, have been implicated in the development of several malignancies, including breast cancer. The interconnections between miRNAs and Hippo signaling pathway core proteins in the breast, on the other hand, remain poorly understood. In this review, we focused on highlighting the Hippo signaling system, its key parts, its importance in breast cancer, and its regulation by miRNAs and other related pathways

Forced orientation of graphs

The concept of forced orientation of graphs was introduced by G. Chartrand et al. in 1994. If, for a given assignment of directions to a subset S of the edges of a graph G, there exists an orientation of E(G) \ S, so that the resulting graph is strongly connected, then that given assignment is said to be extendible to a strong orientation of G. The forced strong orientation number fD(G), with respect to a strong orientation D of G, is the smallest cardinality among the subsets of E(G) to which the assignment of orientations from D, can be uniquely extended to E. We use the term defining set instead of “forced orientation ” to be consistent with similar concepts in other combinatorial objects. It is shown that any minimal strong orientation defining set is also smallest. We also study Spec(G), the spectrum of G, as the set of all possible values for fD(G), where D is taken over all strong orientations of G. Key words: Forced orientation; defining set; strong orientation; algorithms; matroids. 1 Introduction an

The importance of hsa-miR-28 in human malignancies

MicroRNA production in tumorigenesis is dysregulated by a variety of processes, such as proliferation and removal of microRNA genes, aberrant transcriptional regulation of microRNAs, disrupted epigenetic alterations, and failures in the miRNA biogenesis machinery. Under some circumstances, miRNAs may act as tumorigenic and maybe anti-oncogenes. Tumor aspects such as maintaining proliferating signals, bypassing development suppressors, delaying apoptosis, stimulating metastasis and invasion, and promoting angiogenesis have been linked to dysfunctional and dysregulated miRNAs. MiRNAs have been found as possible biomarkers for human cancer in a great deal of research, which requires additional evaluation and confirmation. It is known that hsa-miR-28 can function as an oncogene or tumor suppressor in many malignancies, and it does this by modulating the expression of several genes and the downstream signaling network. MiR-28–5p and miR-28–3p, which originate from the same RNA hairpin precursor miR-28, have essential roles in a variety of cancers. This review outlines the function and mechanisms of miR-28–3p and miR-28–5p in human cancers and illustrates the miR-28 family's potential utility as a diagnostic biomarker for prognosis and early detection of cancers

Safflower Seed Oil, Containing Oleic Acid and Palmitic Acid, Enhances the Stemness of Cultured Embryonic Neural Stem Cells through Notch1 and Induces Neuronal Differentiation

Embryonic neural stem cells (eNSCs) could differentiate into neurons, astrocytes and oligodendrocytes. This study was aimed to determine the effect of safflower seed oil, which contains linoleic acid (LA), oleic acid (OA), and palmitic acid (PA), on cultured eNSC proliferation and differentiation, in comparison to linoleic acid alone. Results showed that safflower seed oil, but not LA, increased significantly the viability and proliferation of eNSCs. Moreover, treatment of NSCs by safflower seed oil, but not LA, resulted in a significant increase in mRNA levels of notch1, hes1, and Ki-67, and protein levels of notch intracellular domain (NICD), in comparison to controls, indicating an enhancement of stemness. Finally, safflower seed oil, but not LA, caused an increase in the number of oligodendrocytes (MBP+), astrocytes (GFAP+) and neurons (β-III tubulin+) of which only the increase in β-III tubulin positive cells was statistically significant. In summary, OA and PA, present in safflower seed oil may prove beneficial for the enhancement of eNSCs and their neuronal differentiation

Preparation and Skin Permeation Study of N, N- Diethyl- meta-Toluamide Semi Solid Formulations

N,N-Diethyl meta Toluamide (DEET) is an insect repellent agent that contrary to its benefits, if is used in formulations with high skin permeation, will produce side effects of different severity. This study attempted to achieve a semi-solid DEET containing formulation with good appearance, sufficient spreadity, suitable viscosity for tube and jar filling, compatible pH with skin, reasonable stability, longer release time, and the less skin permeation. To obtain such a formulation, three types of DEET containing semi solids including gels (hydrophile), creams (emulsion) and ointments (lipophile), and their characteristics were compared with each other and with Off! Brand. Results showed that one of the prepared creams with the proper viscosity, stability, appearance and spreadity, had the least drug release in six hours and less skin permeation of DEET as compared with Off!. Hence the preparation was introduced as the optimal formulation

DataSheet_1_Autoimmunity in monogenic combined immune deficiencies with associated or syndromic features.docx

BackgroundCombined immune deficiencies (CIDs) with associated or syndromic features are a highly heterogeneous subgroup of inherited immune disorders. These patients represent specific clinical complications with an increased risk of autoimmune conditions.MethodsWe analyzed data of monogenic patients with syndromic CIDs adopted from the Iranian inborn errors of immunity registry up to January 2022. A comprehensive comparison in terms of demographic, clinical, and immunological features was performed between patients with and without autoimmunity and also among four mutation groups with the most registered cases including ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations.ResultsA total of 137 patients with monogenic syndromic CIDs were included. Most commonly mutated genes were the ATM [80 (58.4%)] and STAT3 (AD-LOF) [19 (13.9%)], followed by DNMT3B [11 (8%)], and WAS [11 (8%)]. More than 18% of all patients with syndromic CIDs, including most DNMT3B/ZBTB24 mutations patients, were clinically diagnosed with antibody deficiencies before genetic evaluation. Patients with ATM and WAS mutations had the latest age of onset and the lowest age of diagnosis, respectively. Autoimmune disorders were diagnosed in 24 patients at a median age of 3.5 (2.6-6.0) years, 70.6% of which were diagnosed prior to the diagnosis of immunodeficiency. Lymphoproliferation, particularly hepatosplenomegaly, was significantly higher in patients with autoimmunity (p=0.004). Syndromic CID patients with autoimmunity had significantly lower IgG levels. Hematologic autoimmunity mainly immune thrombocytopenic purpura was the most frequent autoimmunity among major groups of ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations, however ATM-mutated patients present more diversified involved organs including rheumatologic, gastrointestinal and dermatologic autoimmunity.ConclusionAbout 18% of patients with monogenic syndromic CIDs developed autoimmunity, mainly in the form of hematological immune diseases. Autoimmunity could be an early-onset involvement with a potential diagnostic impact on suspicious cases of syndromic CIDs.</p