Mohamed Hosney

Background: Doxorubicin (DOX) is an effective chemotherapeutic drug, but its clinical use is limited by dose-dependent cardiotoxicity and cardiomyopathy. Adipose-derived mesenchymal stem cells (ADMSCs) may offer cardioprotective effects through regenerative, antioxidant, and immunomodulatory mechanisms. This study investigated the therapeutic potential of ADMSCs in DOX-induced cardiomyopathy in rats, with focus on miR-146a expression and transcriptional modulation of the NF-κB/TLR-4 inflammatory signaling axis. NF-κB was selected because it plays a central role in regulating inflammatory signaling and is well established as a key link between oxidative stress and myocardial injury in doxorubicin-induced cardiotoxicity, compared with other downstream apoptotic pathways. Methodology: Forty male rats were assigned to control and DOX-treated groups. Cardiomyopathy was induced by intraperitoneal DOX injection at 2.5 mg/kg every other day for 14 days, for a total of seven injections and a cumulative dose of 17.5 mg/kg. During the therapeutic phase, ADMSCs were administered intravenously. Serum creatine kinase activity, cardiac oxidative stress markers, miR-146a, NF-κB, and TLR-4 expression were assessed. Alkaline and neutral comet assays, histopathological examination, and ADMSC homing evaluation were also performed. Results: DOX administration increased serum creatine kinase activity and malondialdehyde levels, reduced catalase activity, and induced cardiac DNA damage and histopathological alterations. Molecular analysis showed a slight, non-significant downward trend in miR-146a expression during induction, together with significant upregulation of NF-κB and TLR-4 expression. ADMSC treatment ameliorated several DOX-associated biochemical, molecular, genotoxic, and histopathological alterations. However, some physiological parameters showed only partial or non-significant improvement. Conclusion: These findings suggest that ADMSCs may attenuate DOX-induced cardiomyopathy, at least partly, through reduced oxidative stress and DNA damage, improved myocardial histology, and transcriptional modulation of the miR-146a/NF-κB/TLR-4 axis.

Understanding the distinctive immunomodulatory processes of the breast cancer microenvironment will be crucial for the creation of novel therapeutic approaches. Cav-1's role in BC is still debated because it has been demonstrated to have a dual opposing role, functioning as both an oncogene and a tumor suppressor. Various studies reported the occurrence of a somatic mutation in Cav-1 in patients' primary breast tumors leading to the substitution of a proline amino acid-to-leucine at 132 (P132L) location. Therefore, the current study aims to examine the expression of Cav-1 in tissue samples of patients with breast cancer and assess the incidence of p132L point mutation of the Cav-1 gene in patients with breast cancer. The current study enrolled 50 patients with breast cancer, and the levels of expression of Cav-1 protein were measured by immunohistochemistry. Sequencing of amplified Cav-1 gene in sample groups was done to assess the incidence of a spontaneous mutation (P132L) inside the human Cav-1 in breast cancer patients. The current results demonstrated the absence of P132L target point mutation in all Cav-1 downregulated Egyptian breast cancer patients (90%). Accordingly, the alteration in the expression level of Cav-1 in tissues of Egyptian patients with breast cancer is not due to the P132L target point mutation, but other factors may contribute to this down-expression.

Background: A large class of proteolytic enzymes known as cysteine cathepsins are created as pro-enzymes and are activated in slightly acidic conditions. They are crucial for both healthy cellular function and illness. Cysteine cathepsins are a family of proteases that play important roles in a variety of cellular processes, including protein turnover, cell adhesion, and migration. Main body: In breast cancer, cysteine cathepsins have been shown to be overexpressed in tumor cells and to be associated with poor prognosis. This review article discusses the role of cysteine cathepsins in breast cancer, focusing on their diagnostic potential. The article provides an overview of cysteine cathepsins, including their structure, function, and regulation in addition to the evidence for the overexpression of cysteine cathepsins in breast cancer and their association with a poor prognosis. Conclusions: The current review demonstrates the potential use of cysteine cathepsins as biomarkers for early detection and diagnosis of breast cancer.

Numerous different cell groups, such as endothelial cells, pericytes, macrophages, mesenchymal stem cells, smooth muscle cells, and stromal fibroblasts, can be found in the tumor microenvironment Caveolin-1, which is also referred to as caveolin, Cav-1, or VIP21 is a structural membrane protein that has been demonstrated to suppress breast tumor growth and metastasis. Numerous studies have determined Cav-1 as a potential therapeutic target for breast cancer due to its inhibitory effects on cancer-associated pathways. In preclinical studies, expressed Cav-1 has been demonstrated to prevent breast tumor cell invasion, and the lack of stromal Cav-1 is linked to early breast cancer development. According to certain research, Cav-1 may also inhibit the late phase of autophagy via HIF-1 in triple-negative breast cancer. Furthermore, Cav-1 has been demonstrated to prevent breast tumor stem cells' self-renewal ability and aerobic glycolysis activity. These data show that Cav-1 may play an important function in breast tumor inhibition, as a possible target for treatment of breast cancer.

Background: Thousands of people have already died as a result of the 2019 coronavirus disease pandemic (COVID-19), which was brought on by the SARS-CoV-2 coronavirus. There were many unimaginable cases of illness in Washington in 2020 as a first case, and then it was transmitted to Wuhan, Germany, France, Italy, Spain, the United Kingdom and China. The newly discovered SARS-CoV, MERS-CoV, and SARS-CoV-2 are believed to be natural and not laboratory synthetic. The COVID-19 pandemic may be due to the contamination of infected people and objects with infected materials that spread across the world.Main body: Human COVID-19 infection symptoms can range from being asymptomatic to being fatal, including respiratory failure, multiple organ dysfunction, and death. Large-scale genetic association studies have demonstrated that immune system components such as interferons, interleukins, toll-like receptors, and human leukocyte antigen as well as COVID-19 receptor variations (angiotensin-converting enzymes, transmembrane serine protease-2) are important host determinants of COVID-19 severity. Conclusion: The current review aims to demonstrate the human genetic factors that affect COVID-19 severity.

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.

Premature ovarian failure (POF) is a disorder that occurs before the age of 40 among women and characterized by amenorrhea. POF usually occurs due to autoimmune disorders, X-chromosome disorders, viral infections, or after chemotherapeutic treatment. POF can be discovered either by histopathology or by using molecular techniques such as real-time PCR to measure the expression of miRNAs that has a role in POF development. Cyclophosphamide (CP) is a well-known chemotherapy used in the treatment of leukemia, lymphoma, and breast cancer, but it has many harsh side effects on many body organs such as the heart, liver, and gonads, especially after high doses administration. Cyclophosphamide-induced POF usually ends with a loss of follicles and granulose cell damage. Herbal medicine is the promising therapeutic approach of POF especially because of its great safety, availability, and low cost. Moringa oleifera (MO) is a plant distributed all around the world; cultivated in tropical and subtropical areas. It has antioxidant and antimicrobial activity and high nutritional and medicinal values and it is also used in different industries as cosmetics and lubricants for machines. Different parts of its plant are used in the treatment of edema, skin infections, inflammations, rheumatism, fever, anemia, bronchitis, and digestive problems. Furthermore, MO has a great promising effect on treating the toxicity of ovaries caused by chemotherapy or heavy metals. On the other side, Withania somnifera (Ashwagandha) is also a herb with great medical importance that is cultivated in tropical and sub-tropical countries, and it has anti-cancer activities, anti-inflammatory and antimicrobial activities. It plays a role in regulating the hormonal balance and enhancing the gonads activity by increasing the ovaries’ weight. It enhances immunity due to its high antioxidant activities. Ashwagandha can reduce stress, anxiety, and depression. Furthermore, it can reduce the symptoms of COVID-19. The leaves and roots are used in treating fever and joint inflammation, and roots have also been nominated among the drugs that neutralize the effect of snake venom.

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.