The present study aimed to investigate the potential role of leptin in the progression of breast cancer and the associated cell proliferation signalling pathway(s). A total of 44 female patients diagnosed with breast cancer and 24 healthy donors from Ain Shams University Hospitals (Cairo, Egypt) were enrolled in the present study. The present study assessed leptin expression in breast cancer tissues at the gene and protein level using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and immunohistochemistry. The results demonstrate that the expression of leptin was significantly higher in tissue of breast cancer samples from obese patients than overweight and control samples (P<0.001). ELISA results indicated a significant increase (P<0.001) of leptin expression in obese patients. To investigate whether there is any difference in leptin expression between the peripheral and tumor microenvironment blood of patients with breast cancer, the concentration of leptin was assessed in plasma from both using ELISA assays. The results demonstrated a statistically significant increase in the level of leptin in plasma samples from the tumor microenvironment of obese patients with estrogen receptor positive (ER+) breast cancer, compared with peripheral plasma samples. Furthermore, the leptin gene was overexpressed in obese ER+ breast cancer tissue. RT‑qPCR was also performed to assess the expression of genes involved in proliferation pathways including leptin receptor (LEPR), aromatase, mitogen activated protein kinase (MAPK) and signal transducer and activator of transcription‑3 (STAT3). A positive association between leptin expression, LEPR, aromatase, MAPK and STAT3 was detected in tissue samples of patients with breast cancer. The current study concluded that leptin may enhance breast cancer progression by inducing the expression of JAK/STAT3, ERK1/2 and estrogen pathways in obese patients breast cancer.

Tumor-associated macrophages (TAMs) promote tumor advancement in many ways, such as inducing angiogenesis and the formation of new blood vessels that provide tumors with nourishment and oxygen. TAMs also facilitate tumor invasion and metastasis by secreting enzymes that degrade the extracellular matrix and generating pro-inflammatory cytokines that enhance the migration of tumor cells. TAMs also have a role in inhibiting the immune response against malignancies. To accomplish this, they release immunosuppressive cytokines such as IL-10, and TAMs can hinder the function of T cells and natural killer cells, which play crucial roles in the immune system's ability to combat cancer. The role of TAMs in breast cancer advancement is a complex and dynamic field of research. Therefore, TAMs are a highly favorable focus for innovative breast cancer treatments. This review presents an extensive overview of the correlation between TAMs and breast cancer development as well as its role in the tumor microenvironment (TME) shedding light on their impact on tumor advancement and immune evasion mechanisms. Notably, our study provides an innovative approach to employing nanomedicine approaches for targeted TAM therapy in breast cancer, providing an in-depth overview of recent advances in this emerging field.

Alzheimer’s disease (AD) is one of the most common causes of dementia. Several drugs are used to improve the symptoms, but do not stop AD progression. There are more promising treatments that may have a significant role in AD diagnosis and treatment such as miRNAs and stem cells. The present study aims to develop a new approach for AD treatment by mesenchymal stem cells (MSCs) and/or acitretin with special reference to inflammatory signaling pathway as NF-kB and its regulator miRNAs in AD-like rat model. Fourty-five male albino rats were allotted for the present study. The experimental periods were divided into induction, withdrawal, and therapeutic phases. Expression levels of miR-146a, miR-155, necrotic, growth and inflammatory genes were assessed using RT-qPCR. Histopathological examination of brain tissues was performed in different rat groups. The normal physiological, molecular, and histopathological levels were restored after treatment with MSCs and/or acitretin. The present study demonstrates that the miR-146a and miR-155 might be used as promising biomarkers for AD. MSCs and/or acitretin proved their therapeutic potential in restoring the expression levels of targeted miRNAs and their related genes concerning NF-kB signaling pathway.

Alzheimer’s disease (AD) is a cumulative progressive neurodegenerative disease characterized mainly by impairment in cognitive functions accompanied by memory loss, disturbance in behavior and personality, and difficulties in learning. Although the main causes of AD pathogenesis are not fully understood yet, amyloid-β peptides and tau proteins are supposed to be responsible for AD onset and pathogenesis. Various demographic, genetic, and environmental risk factors are involved in AD onset and pathogenesis such as age, gender, several genes, lipids, malnutrition, and poor diet. Significant changes were observed in microRNA (miRNA) levels between normal and AD cases giving hope for a diagnostic procedure for AD through a simple blood test. As yet, only two classes of AD therapeutic drugs are approved by FDA. They are classified as acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists (NMDA). Unfortunately, they can only treat the symptoms but cannot cure AD or stop its progression. New therapeutic approaches were developed for AD treatment including acitretin due to its ability to cross blood-brain barrier in the brain of rats and mice and induce the expression of ADAM 10 gene, the α-secretase of human amyloid-β protein precursor, stimulating the non-amyloidogenic pathway for amyloid-β protein precursor processing resulting in amyloid-β reduction. Also stem cells may have a crucial role in AD treatment as they can improve cognitive functions and memory in AD rats through regeneration of damaged neurons. This review spotlights on promising diagnostic techniques such as miRNAs and therapeutic approaches such as acitretin and/or stem cells keeping in consideration AD pathogenesis, stages, symptoms, and risk factors.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by progressive cognitive deterioration. All recent therapeutic strategies tend to inhibit the generation of the Aβ peptide. These approaches tend to mediate both α- and γ-secretases to undergo the nonamyloidogenic pathway. ADAM10 is the main α-secretase that cleaves APP, and it is regulated by the metabolic product of vitamin A (retinoic acid), which is being widely used recently in AD research as a target for treatment. Mesenchymal stem cells (MSCs) are also used recently as a promising regenerative therapy for AD. Objectives: The present study aimed to: (1) study the effect of MSCs with/without acitretin on the regulation of Adam10 gene expression in AlCl3-induced AD rat model, and (2) validate the hypothesis that AD is a time-dependent progressive disease that spreads spontaneously even after the stopping of exposure to AlCl3. Methods: The experimental work has been designed to include three successive phases; AlCl3 induction phase (I), AlCl3 withdrawal phase (W), and therapeutic phase (T). Forty-five male albino Wistar rats were randomly divided into 2 main groups: the control (C) group (15 rats) and AD group (30 rats). The therapeutic potential of MSCs with/without acitretin has been evaluated at behavioral, physiological, molecular, and histopathological levels. Results: Among the three therapeutic groups, combined administration of both MSC and acitretin showed the best compensatory effects on most of the measured parameters. Conclusion: The present study approved that AD is a time-dependent progressive disease which spreads spontaneously without more AlCl3 exposure.