Biocompatibility profile of aged pigmented and non-pigmented silicone elastomer for combined maxillofacial defects.

PURPOSE: To assess the biocompatibility of platinum silicone elastomer A-2000 used in combined maxillofacial defects prosthesis, after being deteriorated by an accelerated aging process resembling both the extra and intraoral environment. This assessment was done indirectly on human-derived dermal and gingival tissues. MATERIALS AND METHODS: One hundred eight samples of room-temperature vulcanized A-2000 platinum silicone were equally divided into extrinsically pigmented and non-pigmented groups to replicate combined maxillofacial defects. Accelerated aging was applied to pigmented samples to mimic extra- and intra-oral conditions, while non-aged counterparts served as controls. After isolating human cell lineages, dermal and gingival fibroblasts were indirectly exposed to silicone sample media. Cytotoxicity to cultured fibroblasts was assessed via MTT assay. Statistical significance was determined by repeated measures of one-way ANOVA (p < 0.01), evaluating cytotoxicity on dermal and gingival fibroblasts. RESULTS: MTT assay showed increased cytotoxicity in pigmented silicon samples subjected to extraoral aging compared to non-aged counterparts (p < 0.01). Non-pigmented silicon, modeling intraoral conditions, exhibited cytotoxicity after 48 h (p < 0.05). Both aged and non-aged silicon extracts equally sensitized gingival fibroblasts at 72 h (p < 0.001). Negative correlations between pigmented and non-pigmented silicon were observed in dermal cell growth (p > 0.05, except at 24 h, r = 0.2), with accelerated aging showing minimal impact on the pigmentation effect (p > 0.05). CONCLUSION: The retrieved diminished cellular metabolic activity of platinum silicone elastomer was in an acceptable clinical range, pointing out the importance of periodic assessments of the maxillofacial prosthesis for replacement depending on aging and cytotoxic harmful cellular responses.

Brain-targeted Tet-1 peptide-PLGA nanoparticles for berberine delivery against STZ-induced Alzheimer's disease in a rat model: Alleviation of hippocampal synaptic dysfunction, Tau pathology, and amyloidogenesis.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that causes severe dementia and memory loss. Surface functionalized poly(lactic-co-glycolic acid) nanoparticles have been reported for better transport through the blood-brain barrier for AD therapy. This study investigated the improved therapeutic potential of berberine-loaded poly(lactic-co-glycolic acid)/Tet-1 peptide nanoparticles (BBR/PLGA-Tet NPs) in a rat model of sporadic AD. BBR was loaded into the PLGA-Tet conjugate. BBR/PLGA-Tet NPs were physicochemically and morphologically characterized. AD was achieved by bilateral intracerebroventricular (ICV) injection of streptozotocin (STZ). Cognitively impaired rats were divided into STZ, STZ + BBR, STZ + BBR/PLGA-Tet NPs, and STZ + PLGA-Tet NPs groups. Cognitive improvement was assessed using the Morris Water Maze. Brain acetylcholinesterase and monoamine oxidase activities, amyloid ß42 (Aß42), and brain glycemic markers were estimated. Further, hippocampal neuroplasticity (BDNF, pCREB, and pERK/ERK), Tau pathogenesis (pGSK3ß/GSK3ß, Cdk5, and pTau), inflammatory, and apoptotic markers were evaluated. Finally, histopathological changes were monitored. ICV-STZ injection produces AD-like pathologies evidenced by Aß42 deposition, Tau hyperphosphorylation, impaired insulin signaling and neuroplasticity, and neuroinflammation. BBR and BBR/PLGA-Tet NPs attenuated STZ-induced hippocampal damage, enhanced cognitive performance, and reduced Aß42, Tau phosphorylation, and proinflammatory responses. BBR/PLGA-Tet NPs restored neuroplasticity, cholinergic, and monoaminergic function, which are critical for cognition and brain function. BBR/PLGA-Tet NPs may have superior therapeutic potential in alleviating sporadic AD than free BBR due to their bioavailability, absorption, and brain uptake.

Antineoplastic drugs inducing cardiac and vascular toxicity - An update.

With the improvement in cancer prognosis due to advances in antitumor therapeutic protocols and new targeted and immunotherapies, we are witnessing a growing increase in survival, however, at the same timeincrease in morbidity among cancer survivors as a consequences of the increased cardiovascular adverse effects of antineoplastic drugs. Common cardiovascular complications of antineoplastic therapies may include cardiac complications such as arrhythmias, myocardial ischemia, left ventricular dysfunction culminating in heart failure as well as vascular complications including arterial hypertension, thromboembolic events, and accelerated atherosclerosis. The toxicity results from the fact that these drugs not only target cancer cells but also affect normal cells within the cardiovascular system. In this article, we review the clinical features and main mechanisms implicated in antineoplastic drug-induced cardiovascular toxicity, including oxidative stress, inflammation, immunothrombosis and growth factors-induced signaling pathways.

Engineering tanshinone-loaded, levan-biofunctionalized polycaprolactone nanofibers for treatment of skin cancer.

Skin cancer is a challenging condition of the highest prevalence rate among other types of cancer. Thus, advancement of local therapeutic approaches for skin cancer is highly needed. Recently, the use of phytotherapeutics, like tanshinone IIA (Tan), as anticancer agents has become promising. In this work, we engineered Tan-loaded polycaprolactone nanofibers, biofunctionalized with levan and egg-lecithin (Tan@Lev/EL/PCL-NF) for local skin cancer therapy. Novel Tan@Lev/EL/PCL-NF were prepared using w/o-emulsion electrospinning, employing a 23-factorial design. Composite NF exhibited nanofiber diameter (365.56 ± 46.25 nm), favorable surface-hydrophilicity and tensile strength. Tan@Lev/EL/PCL-NF could achieve favorably controlled-release (100% in 5 days) and Tan skin-deposition (50%). In vitro anticancer studies verified prominent cytotoxicity of Tan@Lev/EL/PCL-NF on squamous-cell-carcinoma cell-line (SCC), with optimum cytocompatibility on fibroblasts. Tan@Lev/EL/PCL-NF exerted high apoptotic activity with evident nuclear fragmentation, G2/M-mitosis cell-cycle-arrest and antimigratory efficacy. In vivo antitumor activity was established in mice, confirming pronounced inhibition of tumor-growth (224.25 ± 46.89%) and relative tumor weight (1.25 ± 0.18%) for Tan@Lev/EL/PCL-NF compared to other groups. Tan@Lev/EL/PCL-NF afforded tumor-biomarker inhibition, upregulation of caspase-3 and knockdown of BAX and MKi67. Efficient anticancer potential was further confirmed by histomorphometric analysis. Our findings highlight the promising anticancer functionality of composite Tan@Lev/EL/PCL-NF, as efficient local skin cancer phytotherapy.

Targeted Fisetin-Encapsulated ß-Cyclodextrin Nanosponges for Breast Cancer.

Fisetin (FS) is considered a safer phytomedicine alternative to conventional chemotherapeutics for breast cancer treatment. Despite its surpassing therapeutic potential, its clinical utility is hampered by its low systemic bioavailability. Accordingly, as far as we are aware, this is the first study to develop lactoferrin-coated FS-loaded ß-cyclodextrin nanosponges (LF-FS-NS) for targeted FS delivery to breast cancer. NS formation through cross-linking of ß-cyclodextrin by diphenyl carbonate was confirmed by FTIR and XRD. The selected LF-FS-NS showed good colloidal properties (size 52.7 ± 7.2 nm, PDI < 0.3, and ζ-potential 24 mV), high loading efficiency (96 ± 0.3%), and sustained drug release of 26 % after 24 h. Morphological examination using SEM revealed the mesoporous spherical structure of the prepared nanosponges with a pore diameter of ~30 nm, which was further confirmed by surface area measurement. Additionally, LF-FS-NS enhanced FS oral and IP bioavailability (2.5- and 3.2-fold, respectively) compared to FS suspension in rats. Antitumor efficacy evaluation in vitro on MDA-MB-231 cells and in vivo on an Ehrlich ascites mouse model demonstrated significantly higher activity and targetability of LF-FS-NS (30 mg/kg) compared to the free drug and uncoated formulation. Consequently, LF-FS-NS could be addressed as a promising formulation for the effective management of breast cancer.

Biological effect of bone marrow mesenchymal stem cell- derived extracellular vesicles on the structure of alveolar bone in rats with glucocorticoid-induced osteoporosis.

BACKGROUND: Glucocorticoids are used for the treatment of autoimmune disorders; however, they can elicit several side effects such as osteoporosis. Several approaches can be made to treat glucocorticoid-induced osteoporosis, including the use of stem cells. However, the therapeutic effect of mesenchymal stem cells depends on its released factors, including extracellular vesicles. Extracellular vesicles have been recognized as important mediators of intercellular communication as they participate in many physiological processes. The present study was designed to investigate the effect of bone marrow mesenchymal stem cells derived extracellular vesicles on the structure of alveolar bone in rats with glucocorticoid-induced osteoporosis. METHODS: Thirty adult albino male rats were divided into 3 groups: control group (CG), glucocorticoid-induced osteoporosis (GOG) and extracellular vesicles treated group (ExTG). Rats in the GOG and ExTG groups were injected with methylprednisolone acetate (40 mg/kg) intramuscularly in the quadriceps muscle 3 times per week for three weeks in the early morning. Afterwards, the rats in GOG group received a single vehicle injection (PBS) while each rat in the ExTG group received a single injection of extracellular vesicles (400 µg/kg suspended in 0.2 ml PBS) in the tail vein. Rats were euthanized 1 month after injection. Mandibles were dissected and the molar segments were prepared for histological preparation, scanning electron microscopy (SEM), and energy dispersive x-ray (EDX). RESULTS: Histology and scanning electron microscopyof bone tissue showed alveolar bone loss and bone resorption in the GOG group. while in the ExTG group, alveolar bone demostrated normal bone architecture. EDX showed that calcium percentage in GOG group was lower than ExTG group,which showed no statistically significant difference from the control group. CONCLUSIONS: Extracellular vesicles may be a promising treatment modality in the treatment of bone diseases and in bone regeneration. However, further research is needed before stating that extracellular vesicles s can be used to treat bone disorders especially when translating to humans.

Luteolin-loaded exosomes derived from bone marrow mesenchymal stem cells: a promising therapy for liver fibrosis.

Liver fibrosis is a global life-threatening disorder with no approved treatment. It leads to serious hepatic complications when progressive, such as cirrhosis and carcinoma. Luteolin (LUT) is a plant flavonoid possessing a promising therapeutic potential in various liver diseases particularly, liver fibrosis. It was reported to have potent anti-inflammatory and antioxidant properties. It also suppresses the proliferation of activated hepatic stellate cells (HSC) and induces their apoptosis. However, its poor aqueous solubility and exposure to metabolism hinder its clinical use. Mesenchymal stem cells (MSCs)-derived exosomes, nano-sized extracellular vesicles, have recently emerged as natural biocompatible drug delivery vehicles permitting efficient drug delivery. Accordingly, the present study aimed for the first time to investigate the potential of bone marrow MSCs-derived exosomes to improve LUTs antifibrotic effectiveness. LUT-loaded exosomes (LUT-Ex) were successfully developed, optimized and subjected to both in vitro and in vivo characterization. The elaborated LUT-Ex presented good colloidal properties (size; 150 nm, PDI; 0.3 and ζ-potential; -28 mV), typical vesicular shape, reasonable drug entrapment efficiency (40%) with sustained drug release over 72 h. Additionally, the cellular uptake study of coumarin-6-loaded exosomes in HEP-G2 revealed a significant enhancement in their uptake by 78.4% versus free coumarin-6 solution (p ≤ 0.001). Following a single intraperitoneal injection, LUT-Ex revealed a superior antifibrotic activity compared with either LUT-suspension or blank exosomes as evidenced by the results of biochemical and histopathological evaluation. In conclusion, the elaborated LUT-Ex could be addressed as a promising nanocarrier for effective treatment of liver fibrosis.

Evaluation of the Anti-Cancer Potential of Rosa damascena Mill. Callus Extracts against the Human Colorectal Adenocarcinoma Cell Line.

Chemotherapy is an aggressive form of chemical drug therapy aiming to destroy cancer cells. Adjuvant therapy may reduce hazards of chemotherapy and help in destroying these cells when obtained from natural products, such as medical plants. In this study, the potential therapeutic effect of Rosa damascena callus crude extract produced in vitamin-enhanced media is investigated on colorectal cancer cell line Caco-2. Two elicitors, i.e., L-ascorbic acid and citric acid at a concentration of 0.5 g/L were added to the callus induction medium. Callus extraction and the GC-MS analysis of methanolic crude extracts were also determined. Cytotoxicity, clonogenicity, proliferation and migration of Caco-2 colorectal cancer cells were investigated using MTT cytotoxicity, colony-forming, Ki-67 flow cytometry proliferation and Migration Scratch assays, respectively. Our results indicated that L-ascorbic acid treatment enhanced callus growth parameters and improved secondary metabolite contents. It showed the least IC50 value of 137 ug/mL compared to 237 ug/mL and 180 ug/mL in the citric acid-treated and control group. We can conclude that R. damascena callus elicited by L-ascorbic acid improved growth and secondary metabolite contents as well as having an efficient antiproliferative, anti-clonogenic and anti-migratory effect on Caco-2 cancer cells, thus, can be used as an adjuvant anti-cancer therapy.

Improved oral nutraceutical-based intervention for the management of obesity: pterostilbene-loaded chitosan nanoparticles.

Aim: To formulate and assess the oral anti-obesity effect of polymeric-based pterostilbene (PS)-loaded nanoparticles. Methods: Pterostilbene-hydroxypropyl ß-cyclodextrin inclusion complex loaded in chitosan nanoparticles (PS/HPßCD-NPs) were prepared and characterized in vitro. Cytotoxicity, pharmacokinetics and anti-obesity effects were assessed on Caco-2 cell line and high-fat-diet-induced obesity rat model, respectively. In vivo assessment included histological examination, protein and gene expression of obesity biomarkers in adipose tissues. Results: Safe PS/HPßCD-NPs were successfully prepared with improved bioavailability compared with free PS. PS/HPßCD-NPs showed an improved anti-obesity effect, as supported by histological examination, lipid profile, UCP1 gene expression and protein expression of SIRT1, COX2, IL-6 and leptin. Conclusion: Orally administered PS nanoparticles represent a new and promising anti-obesity strategy owing to the sustainable weight loss and minimal side effects; this may be of great socio-economic impact.

Weight gain or obesity represents a major health risk and leads to diseases including cancer and heart disease. Most anti-obesity medications have significant side effects, and there are notable challenges concerning their availability in the body to produce an effect. Pterostilbene is a herbal drug with beneficial anti-obesity effects. However, it has problems such as poor solubility which restrict its use. The aim of the study was to formulate pterostilbene in a nano-based delivery system and fully characterize its anti-obesity effect when given orally. We evaluated the safety and anti-obesity effects of pterostilbene nanoparticles in cells and in obese rats fed on a high-fat diet. We also looked at how the body absorbs, distributes and gets rid of these nanoparticles. The prepared nanoparticles were nontoxic, with an improved anti-obesity effect; they decreased cholesterol levels and helped in changing white fat (which stores fat) to brown fat (which burns calories). We conclude that the developed pterostilbene nanoparticles, given orally, are a new and promising anti-obesity strategy given their long-lasting effect on weight loss and the minimal side effects. This may be of great economic and societal impact.

Potential effect of amniotic fluid-derived stem cells on hyperoxia-induced pulmonary alveolar injury.

BACKGROUND: With the widespread of Coronavirus Disease 2019 pandemic, in spite of the newly emerging vaccines, mutated strains remain a great obstacle to supportive and preventive measures. Coronavirus 19 survivors continue to face great danger of contacting the disease again. As long as no specific treatment has yet to be approved, a great percentage of patients experience real complications, including among others, lung fibrosis. High oxygen inhalation especially for prolonged periods is per se destructive to the lungs. Nevertheless, oxygen remains the first line support for such patients. In the present study we aimed at investigating the role of amniotic fluid-mesenchymal stem cells in preventing versus treating the hyperoxia-induced lung fibrosis in rats. METHODS: The study was conducted on adult albino rats; 5 pregnant female rats were used as amniotic fluid donors, and 64 male rats were randomly divided into two groups: Control group; where 10 rats were kept in normal atmospheric air then sacrificed after 2 months, and hyperoxia-induced lung fibrosis group, where 54 rats were exposed to hyperoxia (100% oxygen for 6 h/day) in air-tight glass chambers for 1 month, then randomly divided into the following 5 subgroups: Hyperoxia group, cell-free media-treated group, stem cells-prophylactic group, stem cells-treated group and untreated group. Isolation, culture and proliferation of stem cells were done till passage 3. Pulmonary function tests, histological examination of lung tissue under light and electron microscopes, biochemical assessment of oxidative stress, IL-6 and Rho-A levels, and statistical analysis of data were performed. F-test (ANOVA) was used for normally distributed quantitative variables, to compare between more than two groups, and Post Hoc test (Tukey) for pairwise comparisons. RESULTS: Labelled amniotic fluid-mesenchymal stem cells homed to lung tissue. Stem cells administration in the stem cells-prophylactic group succeeded to maintain pulmonary functions near the normal values with no significant difference between their values and those of the control group. Moreover, histological examination of lung tissues showed that stem cells-prophylactic group were completely protected while stem cells-treated group still showed various degrees of tissue injury, namely; thickened interalveolar septa, atelectasis and interstitial pneumonia. Biochemical studies after stem cells injection also showed decreased levels of RhoA and IL-6 in the prophylactic group and to a lesser extent in the treated group, in addition to increased total antioxidant capacity and decreased malondialdehyde in the stem cells-injected groups. CONCLUSIONS: Amniotic fluid-mesenchymal stem cells showed promising protective and therapeutic results against hyperoxia-induced lung fibrosis as evaluated physiologically, histologically and biochemically.

Chitosan-coated bovine serum albumin nanoparticles for topical tetrandrine delivery in glaucoma: in vitro and in vivo assessment.

Glaucoma is one of the leading causes of blindness. Therapies available suffer from several drawbacks including low bioavailability, repeated administration and poor patient compliance with adverse effects thereafter. In this study, bovine serum albumin nanoparticles (BSA-NPs) coated with chitosan(CS) were developed for the topical delivery of tetrandrine (TET) for glaucoma management. Optimized nanoparticles were prepared by desolvation. pH, BSA, CS and cross-linking agent concentrations effects on BSA-NPs colloidal properties were investigated. CS-BSA-NPs with particle size 237.9 nm and zeta potential 24 mV was selected for further evaluation. EE% exceeded 95% with sustained release profile. In vitro mucoadhesion was evaluated based on changes in viscosity and zeta potential upon incubation with mucin. Ex vivo transcorneal permeation was significantly enhanced for CS coated formulation. In vitro cell culture studies on corneal stromal fibroblasts revealed NPs biocompatibility with enhanced cellular uptake and improved antioxidant and anti-proliferative properties for the CS-coated formulation. Moreover, BSA-NPs were nonirritant as shown by HET-CAM test. Also, bioavailability in rabbit aqueous humor showed 2-fold increase for CS-TET-BSA-NPs compared to TET with a sustained reduction in intraocular pressure in a rabbit glaucoma model. Overall, results suggest CS-BSA-NPs as a promising platform for topical ocular TET delivery in the management of glaucoma.

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.

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.

Undaria pinnatifida fucoidan nanoparticles loaded with quinacrine attenuate growth and metastasis of pancreatic cancer.

Pancreatic cancer is a devastating gastrointestinal tumor with limited Chemotherapeutic options. Treatment is restricted by its poor vascularity and dense surrounding stroma. Quinacrine is a repositioned drug with an anticancer activity but suffers a limited ability to reach tumor cells. This could be enhanced using nanotechnology by the preparation of quinacrine-loaded Undaria pinnatifida fucoidan nanoparticles. The system exploited fucoidan as both a delivery system of natural origin and active targeting ligand. Lactoferrin was added as a second active targeting ligand. Single and dual-targeted particles prepared through nanoprecipitation and ionic interaction respectively were appraised. Both particles showed a size lower than 200 nm, entrapment efficiency of 80% and a pH-dependent release of the drug in the acidic environment of the tumor. The anticancer activity of quinacrine was enhanced by 5.7 folds in dual targeted particles compared to drug solution with a higher ability to inhibit migration and invasion of cancer. In vivo, these particles showed a 68% reduction in tumor volume compared to only 20% for drug solution. In addition, they showed a higher animals' survival rate with no hepatotoxicity. Hence, these particles could be an effective option for the eradication of pancreatic cancer cells.

Hybrid bioactive hydroxyapatite/polycaprolactone nanoparticles for enhanced osteogenesis.

Hydroxyapatite nanoparticles (HApN) are largely employed as osteogenic inorganic material. Inorganic/polymeric hybrid nanostructures can provide versatile bioactivity for superior osteogenicity, particularly as nanoparticles. Herein, we present hybrid biomaterial-based hydroxyapatite/polycaprolactone nanoparticles (HAp/PCL NPs) realized using simple preparation techniques to augment HApN osteogenicity. Using wet chemical precipitation, we optimized HApN crystalline properties utilizing a 23-factorial design. Optimized HApN exhibited typical Ca/P elemental ratio with high reaction yield. Surface area analysis revealed their mesoporous nature and high surface area. Hybrid HAp/PCL NPs prepared using direct emulsification-solvent evaporation maintained HApN crystallinity with no observed chemical interactions. To the best of our knowledge, we are the first to elaborate the biocompatibility and osteogenicity of nanoparticulate hybrid HAp/PCL. Hybrid HAp/PCL NPs outperformed HApN regarding mesenchymal cell proliferation and osteodifferentiation with reduction of possible cytotoxicity. Unlike HApN, hybrid HAp/PCL NPs presented moderate expression of early osteogenic markers, Runx-2 and osteopontin and significantly elevated expression of the late osteogenic marker, bone sialoprotein after 10-day culture. Our results indicate that hybrid bioactive HAp/PCL NPs could offer a more prominent osteogenic potential than plain HApN for bone regenerative applications as a standalone nanoplatform or as part of complex engineered systems.

Extracellular vesicles miRNA-21: a potential therapeutic tool in premature ovarian dysfunction.

Chemotherapy induces an irreversible premature ovarian dysfunction (POD). Amniotic fluid mesenchymal stem cells (AFMSCs) can rescue fertility; however, the notion that stem cells can rejuvenate follicles is highly controversial due to the predetermined ovarian reserve. This study aims to isolate AFMSC-derived extracellular vesicles (EVs) and investigate their abundancy for the anti-apoptotic miRNA-21 as a means of ovarian restoration. Female rats were divided into healthy controls and POD-induced groups. The POD induced groups were subdivided into three groups according to the therapies they received: placebo-treated POD, AFMSC and EVs groups. Rats were assessed for serum anti-Müllerian hormone (AMH) levels, ovarian caspase 3 and PTEN protein levels in the ovarian lysate. Total follicular counts (TFCs) were estimated from stained ovarian sections. Functional recovery was investigated through daily vaginal smears and mating trials. In vitro chemical transfection of the AFMSCs with selective miRNA-21 mimics/inhibitors followed by isolation of EVs for therapy was conducted in two additional groups. At the interval points studied, treatment with AFMSCs and EVs equally restored TFC, AMH levels, regular estrous cycles and fruitful conception, while it both diminished caspase 3 and PTEN levels. EVs carrying miRNA-21 mimics recapitulated the short-term effects. Placebo-treated POD or EVs carrying miRNA-21 inhibitors showed augmented ovarian follicular damage demonstrated the low AMH levels, TFC and high levels of PTEN and caspase 3. miRNA-21 allowed regeneration by modulating PTEN and caspase 3 apoptotic pathways. Our findings exemplify that EVs could serve as an innovative cell-free therapeutic tool functioning through their miRNA content and that miRNA-21 has a chief regenerative role through modulating PTEN and caspase 3 apoptotic pathways.

Lactoferrin/Hyaluronic acid double-coated lignosulfonate nanoparticles of quinacrine as a controlled release biodegradable nanomedicine targeting pancreatic cancer.

Quinacrine is an antimalarial drug that was repositioned for treatment of cancer. This is the first work to enhance quinacrine activity and minimize its associated hepatotoxicity via loading into bio-degradable, bio-renewable lignosulfonate nanoparticles. Particles were appraised for treatment of pancreatic cancer, one of the most life-threatening tumors with a five-year survival estimate. Optimum nanocomposites prepared by polyelectrolyte interaction exhibited a particle size of 138 nm, a negative surface charge (-28 mV) and a pH dependent release of the drug in an acidic environment. Ligands used for active targeting (lactoferrin and hyaluronic acid) were added to nanoparticles' surface via layer by layer coating technique. The highest anticancer activity on PANC-1 cells was demonstrated with dual active targeted particles (3-fold decrease in IC50) along with an increased ability to inhibit migration and invasion of pancreatic cancer cells. In vivo studies revealed that elaborated nanoparticles particles showed the highest tumor volume reduction with enhanced survival without any toxicity on major organs. In conclusion, the elaborated nanoparticles could be considered as a promising targeted nanotherapy for treatment of pancreatic cancer with higher efficacy& survival rate and lower organ toxicity.

Comparative Study of the Therapeutic Potential of Mesenchymal Stem Cells Derived from Adipose Tissue and Bone Marrow on Acute Myocardial Infarction Model.

OBJECTIVES: Stem cell therapy is a promising approach in the treatment of acute myocardial infarction (AMI). Mesenchymal stem cells (MSC) from bone marrow (BM-MSC) and adipose tissue (AT-MSC) are attractive and feasible for preclinical and clinical trials. In this study, we compared the therapeutic potential of BM-MSC and AT-MSC in repairing the hearts of rats with isoproterenol (ISO)-induced AMI. METHODS: Forty-two female rats were assigned into two groups; the optimization and the experimental group. The optimization groups were further subdivided into control group and the AMI induced group (using ISO). The experimental group was subdivided into AMI+cell-free media injected in the tail vein, AMI+BM-MSC, and AMI+AT-MSC groups treated with the intravenous injection of their respective cell types. Twenty-eight days after induction, electrocardiogram (ECG) was performed, and heart tissue samples were collected for histological assessment and cells tracing. RESULTS: MSC therapy repaired cardiac functions shown by the restoration of ST segment, QT and QRS intervals in the ECG when compared to the AMI group. Infarct area was significantly decreased, and cardiac tissue regeneration signs were shown on histopathological examination. CONCLUSIONS: Both MSC sources proved to be equally efficient in the assessed parameters.

Bone Marrow-Derived Mesenchymal Stem Cell Potential Regression of Dysplasia Associating Experimental Liver Fibrosis in Albino Rats.

OBJECTIVES: Assessing the therapeutic efficacy of superparamagnetic iron oxide nanoparticles (SPIO) labeled bone marrow-derived mesenchymal stem cells (BM-MSCs) on experimental liver fibrosis and associated dysplasia. MATERIALS AND METHODS: MSCs were obtained from 10 male Sprague-Dawley rats while 50 female rats were divided into control (CG), liver fibrosis (CCL4, intraperitoneal injection of CCl4 for 8 weeks), and CCL4 rats treated with SPIO-labeled MSCs (MSCs/CCl4) with and without continuing CCL4 injection for another 8 weeks. Assessment included liver histopathology, liver function tests, transmission electron microscopic tracing for homing of SPIO-MSCs, immunofluorescence histochemistry for fibrosis and dysplasia markers (transforming growth factor-beta (TGF-ß1), proliferation nuclear antigen (PCNA), glypican 3)), and quantitative gene expression analysis for matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1). RESULTS: SPIO-labeled MSCs were engrafted in the fibrotic liver and the BM/MSCs demonstrated regression for fibrous tissue deposition and inhibition progression of dysplastic changes in the liver of CCl4-treated rats on both the histological and molecular levels. CONCLUSION: BM-MSCs possess regenerative and antidysplastic potentials.

Evaluation of autologous adipose-derived stem cells vs. fractional carbon dioxide laser in the treatment of post acne scars: a split-face study.

BACKGROUND: Scarring is a distressing outcome of acne, as it causes cosmetic and psychological problems to the patients. Unfortunately no single treatment is satisfactory; instead, employing multiple modalities may have better outcome. Autologous adipose tissue-derived adult stem cells (AT-ASCs) and their secretory factors can stimulate collagen synthesis; angiogenesis and migration of fibroblasts thus regenerate damaged tissues. Also, conventional treatments for acne scarring, such as lasers and topical regimens, induce new collagen synthesis via activation of dermal fibroblasts or growth factors. The aim of the study was to verify the effectiveness of AT-ASCs for the treatment of acne scarring vs. the fractional carbon dioxide laser (FxCR). SUBJECTS AND METHODS: Split face comparative study included 10 adult patients with post-acne scars on both sides of the face. One side received AT-ASCs single injection while the other received three sessions of FxCR. Scars were then assessed using the global scoring system Goodman and Baron, scar area percent using NIH ImageJ software and functional assessment by measuring the transepidermal water loss (TEWL) and skin hydration. Both sides were followed for three months. RESULTS: A significant improvement in the degree of scar severity, scar area percent, skin hydration, and TEWL after 3 months of treatment on both sides of the face with insignificant differences between both treatment modalities, provided that AT-ASCs treatment was employed once vs. three sessions of FxCR. CONCLUSION: One injection of AT-ASCs is as effective as three sessions of FxCR in the treatment of atrophic acne scars.