Since an initial diagnosis of Alzheimer disease (AD) in 1907, early detection, was unavailable through 116 years. Up-regulation of V-Ets erythroblastosis virus E26 oncogene homolog 2 (Ets2) is capable to enhance neuronal susceptibility and degeneration. Protein expression (PE) of Ets2 has functional impact on AD and Down's syndrome, with diverse intensity. PE of Ets2 has an influential pathogenic impact on AD. Clinical aspects of neurological disorders directly interact with psychological maladies. However, deterioration requires an early management including programmed based protection.

To include cell biology in neuro-genetics; personalized, prognostics, predictive, preventive, predisposing (5xP) platform, accompanied by stratifying brain channels behavior pre- and post-intervention by light music in the AD-patients.

Include exploration of PE assay and electroencephalography of brain channels. The processes are applied according to: (1) Triangle style, by application of cellular network; and (2) PE assay of Ets2 in the peripheral blood of the patients with AD, by Manual single cell based analysis, and Flow-cytometry. (1) Applying the Genetic counselling and pedigree analysis; (2) considering the psychological status of the referral cases; (3) considering the macro-and/or micro-environmental factors; (4) performing the required Genetics' analysis; and (5) applying the required complementary test(s).

PE of Ets2 has pathogenic role in AD. PE unmasked the nature of heterogeneity/diversity/course of evolution by exploring Ets2, D1853N polymorphism in Ataxia Telangiectasia mutated gene (ATM), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and course of evolution at the single cell level of the brain. Ets2 revealed different cellular behavior in the blood and suggested the strategy as 'Gene Product-Based Therapy' and the personalized managements for the patients. PE reflected weak expression of ATM, mosaic pattern of Ets2; remarkable expression of VEGF and EGF by highlighting an early detective platform, considering circulating neural cells (CNCs) and the required molecular investigation, for the target individual(s) predisposed to AD or other neural disease including brain neoplasia. Brain channels-cooperation with diverse/interactive-ratios lead to strategic balancing for improving the life-quality in AD.

We highlighted application of the single CNCs and correlated Ratio based between Brain channels by providing the 5xP personalized clinical management model for an early detection and therapy of the patients with AD and their targeted/predisposed relatives. Novel-evolutionary/hypothetic/heterogenic-results in brain-channels offer personalizd/constructive markers with unlimited cooperation in health and disease.

Cancer is a major public health issue globally and is one of the leading causes of death. Although available treatments improve the survival rate of some cases, many advanced tumors are insensitive to these treatments. Cancer cell differentiation reverts the malignant phenotype to its original state and may even induce differentiation into cell types found in other tissues. Leveraging differentiation-inducing therapy in high-grade tumor masses offers a less aggressive strategy to curb tumor progression and heightens chemotherapy sensitivity. Differentiation-inducing therapy has been demonstrated to be effective in a variety of tumor cells. For example, differentiation therapy has become the first choice for acute promyelocytic leukemia, with the cure rate of more than 90%. Although an appealing concept, the mechanism and clinical drugs used in differentiation therapy are still in their nascent stage, warranting further investigation. In this review, we examine the current differentiation-inducing therapeutic approach and discuss the clinical applications as well as the underlying biological basis of differentiation-inducing agents.

MYCN Proto-Oncogene, BHLH Transcription Factor (MYCN) has been one of the most studied genes in neuroblastoma. It is known for its oncogenetic mechanisms, as well as its role in the prognosis of the disease and it is considered one of the prominent targets for neuroblastoma therapy. In the present work, we attempted to review the literature, on the relation between MYCN and neuroblastoma from all possible mechanistic sites. We have searched the literature for the role of MYCN in neuroblastoma based on the following topics: the references of MYCN in the literature, the gene's anatomy, along with its transcripts, the protein's anatomy, the epigenetic mechanisms regulating MYCN expression and function, as well as MYCN amplification. MYCN plays a significant role in neuroblastoma biology. Its functions and properties range from the forming of G-quadraplexes, to the interaction with miRNAs, as well as the regulation of gene methylation and histone acetylation and deacetylation. Although MYCN is one of the most primary genes studied in neuroblastoma, there is still a lot to be learned. Our knowledge on the exact mechanisms of MYCN amplification, etiology and potential interventions is still limited. The knowledge on the molecular mechanisms of MYCN in neuroblastoma, could have potential prognostic and therapeutic advantages.

Chemotherapy-induced peripheral neuropathy is not only one of the most common causes of dose reduction or discontinuation of cancer treatment, but it can also permanently decrease the quality of life of cancer patients and survivors. Notably, Sirt2 protects many organs from various injuries, including diabetic peripheral neuropathy. As demonstrated previously by our laboratory and others, the overexpression of Sirt2 can improve cisplatin-induced neuropathy, although the mechanism is still unclear.

In this study, the underlying mechanism by which Sirt2 protects neurons from cisplatin-induced injury was explored using the RNAseq technique in cultured rodent neurons. Sirt2 status was modified by genetic knockout (Sirt2/KO) and was then reconstituted in Sirt2/KO cells (Sirt2/Res). We observed 323 upregulated genes and 277 downregulated genes in Sirt2-expressing cells (Sirt2/Res) compared to Sirt2-deficient cells (Sirt2/KO). Pathway analysis suggested that Sirt2 may affect several pathways, such as MAPK, TNF, and cytokine-cytokine interaction. Furthermore, cisplatin-induced changes to the transcriptome are strongly associated with Sirt2 status. Cisplatin induced distinctive transcriptome changes for 227 genes in Sirt2-expressing cells and for 783 genes in Sirt2-deficient cells, while changes in only 138 of these genes were independent of Sirt2 status. Interestingly, changes in the p53 pathway, ECM-receptor interactions, and cytokine-cytokine receptor interactions were induced by cisplatin only in Sirt2-deficient cells.

This study demonstrated that Sirt2 regulates the transcriptome in cultured rodent neuronal cells. Furthermore, Sirt2-associated transcriptome regulation may be an important mechanism underlying the role of Sirt2 in organ protection, such as in cisplatin-induced neuronal injury. Sirt2 may be a potential target for the prevention and treatment of chemotherapy-induced neuropathy.

Wilms tumor, derived from embryonic cells, accounts for a large proportion of pediatric renal tumors. MYCN encoded by MYCN proto-oncogene, a member of the MYC family, is a BHLH transcription factor. It plays a critical role in tumorigenesis and predicts poor clinical outcomes in various types of cancer. However, the role of MYCN remained unclarified in Wilms tumor. In this study, we investigated the association between MYCN gene polymorphisms and Wilms tumor susceptibility.

Four MYCN gene polymorphisms (rs57961569 G > A, rs9653226 T > C, rs13034994 A > G, and rs60226897 G > A) were genotyped in 183 cases and 603 controls. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated to evaluate the association between MYCN gene polymorphisms and Wilms tumor susceptibility.

Overall, no significant association was found for any of the four MYCN gene polymorphisms. Interestingly, in the stratification analysis, the rs57961569 was found to be associated with decreased Wilms tumor susceptibility in the children older than 18 months (AOR = 0.65, 95% CI = 0.42-1.00, P = .050). Moreover, older children carrying 2-4 risk genotypes were at increased risk of Wilms tumor (OR = 1.55, 95% CI = 1.001-2.40, P = .0497). Haplotype GCAA was shown to significantly increased Wilms tumor risk (AOR = 2.40, 95% CI = 1.12-5.14, P = .024).

Our study demonstrated that these MYCN gene polymorphisms might be low penetrant variants in Wilms tumor.

Meningiomas represent one of the most common brain tumors and exhibit a clinically heterogeneous behavior, sometimes difficult to predict with classic histopathologic features. While emerging molecular profiling efforts have linked specific genomic drivers to distinct clinical patterns, the proteomic landscape of meningiomas remains largely unexplored.

We utilize liquid chromatography tandem mass spectrometry with an Orbitrap mass analyzer to quantify global protein abundances of a clinically well-annotated formalin-fixed paraffin embedded (FFPE) cohort (n = 61) of meningiomas spanning all World Health Organization (WHO) grades and various degrees of clinical aggressiveness.

In total, we quantify 3042 unique proteins comparing patterns across different clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic (n = 106 proteins, Welch's t-test, P < 0.01) and pathway-level (eg, Notch and PI3K/AKT/mTOR) differences between convexity and skull base meningiomas. Supervised comparative analyses of different pathological grades revealed distinct patterns between benign (grade I) and atypical/malignant (grades II‒III) meningiomas with specific oncogenes enriched in higher grade lesions. Independent of WHO grade, clinically aggressive meningiomas that rapidly recurred (<3 y) had distinctive protein patterns converging on mRNA processing and impaired activation of the matrisome complex. Larger sized meningiomas (>3 cm maximum tumor diameter) and those with previous radiation exposure revealed perturbed pro-proliferative (eg, epidermal growth factor receptor) and metabolic as well as inflammatory response pathways (mitochondrial activity, interferon), respectively.

Our proteomic study demonstrates that meningiomas of different grades and clinical parameters present distinct proteomic profiles. These proteomic variations offer potential future utility in helping better predict patient outcome and in nominating novel therapeutic targets for personalized care.

Cisplatin, a commonly used chemotherapeutic agent for glioma patients, treatment often leads to chemoresistance. Accumulating evidence has demosntrated that microRNA (miRNA/miR) is involved in drug resistance of glioma cells. Nevertheless, the role of miR‑501‑3p in glioma cell resistance to cisplatin is unclear. In the present study, it was revealed that miR‑501‑3p expression was decreased in glioma tissues and further underexpressed in cisplatin‑resistant glioma cells compared with wild‑type (WT) glioma cells. Furthermore, cisplatin treatment inhibited the level of miR‑501‑3p in a time‑dependent way. Ectopic expression of miR‑501‑3p suppressed glioma cell growth and invasion, but increased cisplatin‑resistant glioma cell apoptosis. Furthermore, miR‑501‑3p sensitized glioma cells to cisplatin‑induced proliferation arrest and death. Mechanistically, it was demonstrated that miR‑501‑3p targeted MYCN in glioma cells. In addition, it was revealed that miR‑501‑3p inhibited MYCN expression by a luciferase reporter assay and reverse transcription‑quantitative polymerase chain reaction. Notably, restoration of MYCN reversed the effects of miR‑501‑3p in cisplatin‑resistant glioma cells. In conclusion, these results suggested that miR‑501‑3p may serve a promising marker for cisplatin resistance.