A drug repurposing approach of Atorvastatin calcium for its antiproliferative activity for effective treatment of breast cancer: In vitro and in vivo assessment.

Breast cancer, the most common cancer among women, caused over 500,000 deaths in 2020. Conventional treatments are expensive and have severe side effects. Drug repurposing is a novel approach aiming to reposition clinically approved non-cancer drugs into newer cancer treatments. Atorvastatin calcium (ATR Ca) which is used for the treatment of hypercholesterolemia has potential to modulate cell growth and apoptosis. The study aimed at utilizing gelucire-based solid lipid nanoparticles (SLNs) and lactoferrin (Lf) as targeting ligand to enhance tumor targeting of atorvastatin calcium for effective management of breast cancer. Lf-decorated-ATR Ca-SLNs showed acceptable particle size and PDI values <200 nm and 0.35 respectively, entrapment efficiency >90% and sustained drug release profile with 78.97 ± 12.3% released after 24 h. In vitro cytotoxicity study on breast cancer cell lines (MCF-7) showed that Lf-decorated-ATR Ca-SLNs obviously improved anti-tumor activity by 2 to 2.5 folds compared to undecorated ATR Ca-SLNs and free drug. Further, In vivo study was also carried out using Ehrlich breast cancer model in mice. Caspase-3 apoptotic marker revealed superior antineoplastic and apoptosis-inducing activity in the groups treated with ATR Ca-SLNs either decorated/ undecorated with Lf in dosage 10 mg/kg/day p < 0.001 with superior activity for lactoferrin-decorated formulation.

Fucoidan/hyaluronic acid cross-linked zein nanoparticles loaded with fisetin as a novel targeted nanotherapy for oral cancer.

Fisetin (FS) is an anticancer drug having potential role in oral tumors management. However, its clinical application is limited due to its hydrophobicity and instability. Bioactive polymers-based nanosystems have a great potential in cancer therapy. Herein, different biopolymers were selected for their anticancer activity and targeting ability for nanoparticles preparation namely; fucoidan (FU), zein (Zn) and hyaluronic acid (HA). The selected FS-loaded cross-linked Zn nanoparticles (ZFH) which contains HA& FU for Zn nanoparticles stabilization showed the most suitable particle size (196 ± 6.53 nm), mean surface net charge (-38.8 ± 1.47 mV) and entrapment efficiency (98 ± 1.2 %). This is the first study to utilize both HA &FU not only for stabilization but also for dual targeting effect due to their targeting ability to multiple tumor targets. In-vitro anticancer activity of ZHF revealed remarkable uptake by SCC-4 cells with significant cytotoxic action. Further, ZHF was appraised using 4-nitroquinoline 1-oxide (4-NQO)-induced oral cancer in-vivo; ZHF significantly reduced OSCC-specific serum biomarkers levels, histologic tumor grade and increased caspase-3 level. Moreover, potential of destroying two key tumor regulatory cells; TECs and CSCs, was evaluated using their specific markers. The elaborated ZFH nanoparticles could be considered as promising targeted nanotherapy for oral cancer treatment with enhanced efficacy and survival rate.

Effect of Direct Acting Antivirals (DAAs) on Myeloid-Derived Suppressor Cells Population in Egyptian Chronic Hepatitis C Virus Patients: A Potential Immunomodulatory Role of DAAs.

Chronic hepatitis C is a major health concern with high morbidity and mortality rates. The introduction of direct acting antivirals (DAAs) as a first-line treatment for hepatitis C virus (HCV) has significantly enhanced HCV eradication. However, DAA therapy is facing rising concerns regarding long-term safety, viral resistance, and reinfection. HCV is associated with different immune alteration mechanisms that can evade immunity and establish persistent infection. One of these suggested mechanisms is the accumulation of myeloid-derived suppressor cells (MDSCs), which is known to accumulate in chronic inflammatory conditions. Moreover, the role of DAA in restoring immunity after successful viral eradication is still unclear and needs further investigations. Thus, we aimed to investigate the role of MDSCs in chronic HCV Egyptian patients and its response to DAA in treated compared with untreated patients. Fifty untreated chronic hepatitis C (CHC) patients, 50 DAA-treated CHC patients, and 30 healthy individuals were recruited. We used flow cytometer analysis to measure MDSCs frequency and enzyme-linked immunosorbent assay analysis to evaluate the serum level of interferon (IFN)-γ. We found a significant elevation in MDSC% among the untreated group (34.5 ± 12.4%) compared with the DAA-treated group (18.3 ± 6.7%), while the control group had a mean of (3.8 ± 1.6%). IFN-γ concentration was higher in treated patients compared with untreated. We also found a significant negative correlation (rs -0.662) (p < 0.001) between MDSC% and IFN-γ concentration among treated HCV patients. Our results revealed important evidence of MDSCs accumulation in CHC patients and partial retrieval of the immune system regulatory function after DAA therapy.

Photo-excitable zinc sulfide nanoparticles: A theranostic nanotool for cancer management.

OBJECTIVES: Zinc sulfide nanoparticles (ZnS NPs), as one of the quantum dots less than 10 nm, possess unique size-dependent autofluorescence. Excitation of their valence electrons by energy higher than the bandgap reveals the ZnS NPs' inherited photocatalysis with additive cytotoxic consequences of reactive oxygen species (ROS) release. Coupling the cytotoxicity of photoactivated ZnS NPs with their autofluorescence would be a novel theranostic modality, combating superficially accessible carcinoma. MATERIAL AND METHODS: After synthesizing and characterization of ZnS NPs, we verified their photocatalysis and electron donation upon UV excitation in degrading organic dye and DNA cleavage, respectively. We then tested the efficacy of UV-activated ZnS NPs to induce ROS-dependent apoptosis in squamous cell carcinoma and breast cancer cell lines. RESULTS: The energetic electron-hole pairs generated upon UV excitation of ZnS NPs with the consequent cascade of ROS release revealed potent apoptotic cancer cell deaths, compared with single treatment modalities of nonexcited nanoparticles and UV. Moreover, the inherited luminescence of ZnS NPs enabled visualization of their predominant intracytoplasmic uptake with tracking of their cellular response. CONCLUSION: The intensified luminescence and the fortified cytotoxicity of photoactivated ZnS NPs enhance their theranostic qualifications, boosting their antitumorigenic use.

The theranostic potentialities of bioavailable nanocurcumin in oral cancer management.

BACKGROUND: Oral cancer, one of the most common cancers, has unimproved 5-years survival rate in the last 30 years and the chemo/radiotherapy-associated morbidity. Therefore, intervention strategies that evade harmful side effects of the conventional treatment modalities are of need. Herbal therapy as a complementary preventive/therapeutic modality has gained attention. Curcumin is one of the herbal compounds possessing unique anticancer activity and luminescent optical properties. However, its low water solubility limits its efficacy. In contrast, curcumin at the nanoscale shows altered physical properties with enhancing bioavailability. METHODS: The current study evaluated the impact of nanocurcumin as an anti-oral cancer herbal remedy, comparing its efficacy against the native curcumin complement and conventional chemotherapeutic. An optimized polymeric-stabilized nanocurcumin was synthesized using the solvent-antisolvent precipitation technique. After assuring the solubility and biocompatibility of nanocurcumin, we determined its cytotoxic dose in treating the squamous cell carcinoma cell line. We then evaluated the anti-tumorigenic activity of the nano-herb in inhibiting wound closure and the cytological alterations of the treated cancer cells. Furthermore, the cellular uptake of the nanocurcumin was assessed depending on its autofluorescence. RESULTS: The hydrophilic optimized nanocurcumin has a potent cancerous cytotoxicity at a lower dose (60.8 µg/mL) than the native curcumin particles (212.4 µg/mL) that precipitated on high doses hindering their cellular uptake. Moreover, the nanocurcumin showed differential targeting of the cancer cells over the normal fibroblasts with a selectivity index of 4.5. With the confocal microscopy, the luminescent nanoparticles showed gradual nuclear and cytoplasmic uptake with apparent apoptotic cell death, over the fluorescent doxorubicin with its necrotic effect. Furthermore, the nanocurcumin superiorly inhibited the migration of cancer cells by -25%. CONCLUSIONS: The bioavailable nanocurcumin has better apoptotic cytotoxicity. Moreover, its superior luminescence promotes the theranostic potentialities of the nano-herb combating oral cancer.

In vivo bio-distribution and acute toxicity evaluation of greenly synthesized ultra-small gold nanoparticles with different biological activities.

Ultra-small gold nanoparticles (Au-NPs) "≤ 10 nm diameters" have potent biomedical applications. Hence, the present study aimed to greenly synthesize ultra-small gold nanoparticles using Egyptian propolis extract. Different biological activities, in vivo bio-distribution and acute toxicity study were assessed. Results revealed that, Egyptian propolis extract can successfully synthesize the highly pure and stable ultra-small Au-NPs with average diameter 7.8 nm. In vitro antimicrobial and antimycobacterial activities revealed the powerful effect of the prepared Au-NPs. Moreover, the cytotoxic effect on human cancer cell lines revealed the potent inhibition of the cancer cells' proliferation with high reactive oxygen species-mediated apoptosis induction. In vivo bio-distribution and acute toxicity studies were performed (10 and 100 mg/kg doses) in male albino rats. The ultra-small Au-NPs showed low or no toxicity upon using the Au-NPs low dose. The mean area accumulation (%) of the Au-NPs was higher in the liver, kidney, and brain tissues (4.41, 2.96, and 0.3 times, respectively) treated with high Au-NPs dosage compared to those treated with the low dose. Surprisingly, Au-NP accumulation in brain tissue was observed in the glial cells only. Accordingly, the low dose (10 mg/kg) of Au-NPs can be used safely in a variety of biomedical applications.

The potential implications of estrogenic and antioxidant-dependent activities of high doses of methyl paraben on MCF7 breast cancer cells.

Methyl paraben (MP) is an endocrine-disrupting compound that possesses estrogenic properties and contributes to an aberrant burden of estrogen signaling in the human breast and subsequently increasing the risks for the development of breast cancer. The exact exposure, as well as the safe concentrations, are variable among daily products. The present study addresses the effects of exposure to escalated concentrations of MP on the proliferation of MCF-7 breast cancer cells in addition to exploring its other mechanisms of action. The study involved exposure of cultured MCF-7 breast cancer cells to seven MP concentrations, ranging from 40 to 800 µM for 5 days. Cell viability, apoptosis, and proliferation were respectively assessed using crystal violet test, flow cytometric analysis, and quantitative real-time polymerase chain reaction for Ki-67 expression. The estradiol (E2) secretion and oxidative stress were also assessed and analyzed in correlation to MP's proliferation and cytotoxicity potentials. The results showed that the maximum proliferative concentration of MP was 800 µM. At a concentration of 40 µM and higher, MP induced increased expression of Ki-67, denoting enhanced proliferation of the cells in monolayer culture. A positive correlation between the detrimental oxidative stress effect of MP's tested concentrations, cell proliferation, and viability was demonstrated (p < 0.05). Our results indicated that MP at high doses induced sustained cell proliferation due to E2 secretion as well as its antioxidant activity. Accordingly, it was concluded that high and unpredicted exposure to MP might carry a carcinogenic hazard on estrogen receptor-positive breast cancer cells.

Cardiac stem cells: Current knowledge and future prospects.

Regenerative medicine is the field concerned with the repair and restoration of the integrity of damaged human tissues as well as whole organs. Since the inception of the field several decades ago, regenerative medicine therapies, namely stem cells, have received significant attention in preclinical studies and clinical trials. Apart from their known potential for differentiation into the various body cells, stem cells enhance the organ's intrinsic regenerative capacity by altering its environment, whether by exogenous injection or introducing their products that modulate endogenous stem cell function and fate for the sake of regeneration. Recently, research in cardiology has highlighted the evidence for the existence of cardiac stem and progenitor cells (CSCs/CPCs). The global burden of cardiovascular diseases' morbidity and mortality has demanded an in-depth understanding of the biology of CSCs/CPCs aiming at improving the outcome for an innovative therapeutic strategy. This review will discuss the nature of each of the CSCs/CPCs, their environment, their interplay with other cells, and their metabolism. In addition, important issues are tackled concerning the potency of CSCs/CPCs in relation to their secretome for mediating the ability to influence other cells. Moreover, the review will throw the light on the clinical trials and the preclinical studies using CSCs/CPCs and combined therapy for cardiac regeneration. Finally, the novel role of nanotechnology in cardiac regeneration will be explored.