Protective Effect of Zinc Oxide Nanoparticles on Bisphenol S-Induced Cytotoxicity in Human Embryonal Testicular Carcinoma Cell Line.

OBJECTIVE: Bisphenols are a type of phenolic chemical frequently used in producing various consumer products. Owing to their widespread exposure, these compounds can cause multiple toxic effects in humans. This study aimed to assess the protective effects of zinc oxide nanoparticles (ZnONPs) against bisphenol S (BPS)-induced cytotoxicity in the human testicular embryonic carcinoma cell line (NT2/D1). MATERIALS AND METHODS: In this experimental study, cytotoxic concentrations of ZnONPs and BPS on NT2/D1 cells were optimized using the MTT assay. Thereafter, the effects of ZnONPs (50 and 500 µM), BPS (300 and 600 µM), and pre-treatment with ZnONPs (50 µM) followed by exposure to BPS (600 µM) on the expression of SOX2 and OCT4 genes and apoptosis-related proteins (i.e. Bax and Bcl-2) were evaluated, using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, respectively. RESULTS: Both BPS and ZnONPs reduced the viability of NT2/D1 cells in a time- and dose-dependent manner. Pretreatment with 50 µM of ZnONPs increased mRNA levels of SOX2 and OCT4 and improved the reduction of cell viability caused by exposure to half-maximal inhibitory concentration (IC50) of BPS (P<0.001). In addition, pre-treatment with ZnONPs was able to suppress BPS-induced apoptosis, as evidenced by increased Bcl-2 (P<0.05) and decreased Bax (P<0.001) protein levels. CONCLUSION: Although our findings indicate that short-term treatment with a low concentration of ZnONPs could have beneficial effects in preventing the cytotoxic effects of BPS by modulating the expression of apoptosis-related proteins and pluripotent genes in the NT2/D1 cells, further studies are recommended to confirm these results.

Development, Optimization, and in vitro Evaluation of Silybin-loaded PLGA Nanoparticles and Decoration with 5TR1 Aptamer for Targeted Delivery to Colorectal Cancer Cells.

Chemotherapeutic agents often lack specificity, intratumoral accumulation, and face drug resistance. Targeted drug delivery systems based on nanoparticles (NPs) mitigate these issues. Poly (lactic-co-glycolic acid) (PLGA) is a well-studied polymer, commonly modified with aptamers (Apts) for cancer diagnosis and therapy. In this study, silybin (SBN), a natural agent with established anticancer properties, was encapsulated into PLGA NPs to control delivery and improve its poor solubility. The field-emission scanning electron microscopy (FE-SEM) showed spherical and uniform morphology of optimum SBN-PLGA NPs with 138.57±1.30nm diameter, 0.202±0.004 polydispersity index (PDI), -16.93±0.45mV zeta potential (ZP), and 70.19±1.63% entrapment efficiency (EE). The results of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) showed no chemical interaction between formulation components, and differential scanning calorimetry (DSC) thermograms confirmed efficient SBN entrapment in the carrier. Then, the optimum formulation was functionalized with 5TR1 Apt for active targeted delivery of SBN to colorectal cancer (CRC) cells in vitro. The SBN-PLGA-5TR1 nanocomplex released SBN at a sustained and constant rate (zero-order kinetic), favoring passive delivery to acidic CRC environments. The MTT assay demonstrated the highest cytotoxicity of the SBN-PLGA-5TR1 nanocomplex in C26 and HT29 cells and no significant cytotoxicity in normal cells. Apoptosis analysis supported these results, showing early apoptosis induction with SBN-PLGA-5TR1 nanocomplex which indicated this agent could cause programmed death more than necrosis. This study presents the first targeted delivery of SBN to cancer cells using Apts. The SBN-PLGA-5TR1 nanocomplex effectively targeted and suppressed CRC cell proliferation, providing valuable insights into CRC treatment without harmful effects on healthy tissues.

Vitamin K (Menadione)-incorporated chitosan/alginate hydrogel as a novel product for periorbital hyperpigmentation.

The possibility of controlling periorbital hyperpigmentation disorders is one of the most important research goals in cosmetic preparations. In the current investigation, 1% vitamin K (Vit K) was incorporated into a Chitosan/alginate hydrogel which aimed to increase the dermal delivery and anti-pigmentation effect. The Vit K-hydrogel was evaluated using several different tests, including volume expansion/contraction analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), ultraviolet (UV) absorbance spectroscopy, and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Vit K hydrogel's drug release profile showed a steady increase over time. Furthermore, the modified Vit K hydrogel formulations showed no harmful effects in an in vitro cytotoxicity study. The Vit K hydrogel was tested for dermal irritation on Wistar rats, and the hydrogel was found to be non-irritating. Furthermore, Vit K-hydrogel inhibited melanin formation (31.76 ± 1.14%) and was remarkably higher than free Vit K. In addition, Vit K-hydrogel inhibited L-dopa auto-oxidation to a greater extent (94.80 ± 2.41%) in comparison with Vit K solution (73.95 ± 1.62%). Vit K-hydrogel enhanced percutaneous transport of Vit K, according to in vitro percutaneous absorption findings, suggesting that this innovative formulation may provide new therapeutic options for periorbital hyperpigmentation.

Recent advances in novel miRNA mediated approaches for targeting breast cancer.

Breast cancer (BC) is considered one of the most frequent cancers among woman worldwide. While conventional therapy has been successful in treating many cases of breast cancer, drug resistance, heterogenicity, tumour features and recurrence, invasion, metastasis and the presence of breast cancer stem cells can hinder the effect of treatments, and can reduce the quality of life of patients. MicroRNAs (miRNAs) are short non-coding RNA molecules that play a crucial role in the development and progression of breast cancer. Several studies have reported that aberrant expression of specific miRNAs is associated with the pathogenesis of breast cancer. However, miRNAs are emerging as potential biomarkers and therapeutic targets for breast cancer. Understanding their role in breast cancer biology could help develop more effective treatments for this disease. The present study discusses the biogenesis and function of miRNAs, as well as miRNA therapy approaches for targeting and treating breast cancer cells.

Aptamer-functionalized mesenchymal stem cells-derived exosomes for targeted delivery of SN38 to colon cancer cells.

Objectives: Known as natural nanovesicles, exosomes have attracted increased attention as biocompatible carriers throughout recent years, which can provide appropriate sources for incorporating and transferring drugs to desired cells in order to improve their effectiveness and safety. Materials and Methods: This study implicates the isolation of mesenchymal stem cells from adipocyte tissue (ADSCs) to acquire a proper amount of exosomes for drug delivery. As the exosomes were separated by ultracentrifugation, SN38 was entrapped into ADSCs-derived exosomes through the combination method of incubation, freeze-thaw, and surfactant treatment (SN38/Exo). Then, SN38/Exo was conjugated with anti-MUC1 aptamer (SN38/Exo-Apt), and its targeting ability and cytotoxicity towards cancer cells were investigated. Results: Encapsulation efficiency of SN38 into exosomes (58%) was significantly increased using our novel combination method. Furthermore, the in vitro results were indicative of the great cellular uptake of SN38/Exo-Apt and its significant cytotoxicity on Mucin 1 overexpressing cells (C26 cancer cells) without noticeable cytotoxicity on normal cells (CHO cells). Conclusion: The results propose that our approach developed an efficient method for loading SN38 as a hydrophobic drug into exosomes and decorating them with MUC1 aptamer against Mucin 1 overexpressing cells. So, SN38/Exo-Apt could be considered a great platform in the future for the therapy of colorectal cancer.

Efficient Neural Differentiation of Mouse Embryonic Stem Cells by Mastic Gum.

Purpose: Promoting neurogenesis is a promising strategy to treat neurodegenerative disorders. In the present study, we aimed to evaluate the effect of mastic gum resin from the Pistacia lentiscus var. Chia (Anacardiaceae family) in proliferation capacity and differentiation of embryonic mesenchymal stem cells into a neural lineage. Methods: For this purpose, mastic gum was applied as a neural inducer for stem cell differentiation into the neuronal lineage. Following treatment of embryonic stem cells (ESCs) with mastic gum, verification differentiation of the ESCs into the neuronal lineage, gene expression analysis, and immunocytochemistry staining approach were performed. Results: Gene expression analysis demonstrated that mastic gum increased the expression level of neuron markers in the ESCs-derived neuron-like cells. Moreover, our immunocytochemistry staining results of two important neural stem cell markers, including Nestin and microtubule-associated protein-2 (Map2) expression confirmed that mastic gum has the potential to promote neuronal differentiation in ESCs. Conclusion: In summary, the use of mastic gum to stimulate the differentiation of ESCs into a neural lineage can be considered as a good candidate in stem cell therapy.

Targeted delivery of galbanic acid to colon cancer cells by PLGA nanoparticles incorporated into human mesenchymal stem cells.

Objective: The aim of this study was to investigate the efficacy of mesenchyme stem cells (MSCs) derived from human adipose tissue (hMSCs) as carriers for delivery of galbanic acid (GBA), a potential anticancer agent, loaded into poly (lactic-co-glycolic acid) (PLGA) nanoparticles (nano-engineered hMSCs) against tumor cells. Materials and Methods: GBA-loaded PLGA nanoparticles (PLGA/GBA) were prepared by single emulsion method and their physicochemical properties were evaluated. Then, PLGA/GBA nanoparticles were incorporated into hMSCs (hMSC/PLGA-GBA) and their migration ability and cytotoxicity against colon cancer cells were investigated. Results: The loading efficiency of PLGA/GBA nanoparticles with average size of 214±30.5 nm into hMSCs, was about 85 and 92% at GBA concentration of 20 and 40 µM, respectively. Nano-engineered hMSCs showed significant higher migration to cancer cells (C26) compared to normal cells (NIH/3T3). Furthermore, nano-engineered hMSCs could effectively induce cell death in C26 cells in comparison with non-engineered hMSCs. Conclusion: hMSCs could be implemented for efficient loading of PLGA/GBA nanoparticles to produce a targeted cellular carrier against cancer cells. Thus, according to minimal toxicity on normal cells, it deserves to be considered as a valuable platform for drug delivery in cancer therapy.

Effects of Boswellia species on viral infections with particular attention to SARS-CoV-2.

The emergence of pathogenic viruses is a worldwide frequent cause of diseases and, therefore, the design of treatments for viral infections stands as a significant research topic. Despite many efforts, the production of vaccines is faced with many obstacles and the high rate of viral resistance caused a severe reduction in the efficacy of antiviral drugs. However, the attempt of developing novel natural drugs, as well as the exertion of medicinal plants, may be an applicable solution for the treatment of viral diseases. Boswellia species exhibited a wide range of pharmacological activities in various conditions such as bronchial asthma, rheumatism, and Crohn's illness. Additionally, pharmacological studies reported the observance of practical antiviral activities from different parts of this substance, especially the oleo-gum-resin. Therefore, this work provided an overview on the antiviral properties of Boswellia species and their potential therapeutic effects in the field of COVID-19 pandemic.

A dose-related positive effect of inhaled simvastatin-loaded PLGA nanoparticles on paraquat-induced pulmonary fibrosis in rats.

OBJECTIVE: Pulmonary fibrosis is an important complication of subacute paraquat (PQ) poisoning. Here, we reported a novel nanotherapeutic platform for PQ-induced pulmonary fibrosis in animal inhalation models using simvastatin (SV)-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). METHODS AND MATERIALS: Eight inhalations of normal saline, PQ (24 mg/kg), PQ plus SV (20 mg/kg), PQ plus SV-loaded PLGA NPs at doses of 5, 10 or 20 mg/kg or PQ plus PLGA NPs were given to rats. After the end of the treatment period, inflammatory factors and creatine phosphokinase as well as lung pathological changes and tracheal responsiveness were evaluated. RESULTS: Inhalation of SV-loaded PLGA NPs could significantly prevent the progression of PQ-induced pulmonary fibrosis especially at a dose of 10 mg through decreasing the serum level of inflammatory factors as well as contractile responses (p < 0.001) compared to PQ group. Pathological findings also confirmed the results. However, inhalation of non-formulated SV could not prevent tissue damage and fibrosis in comparision with SV-loaded PLGA NPs. CONCLUSION: Taken together, the present work provides us an idea about the pulmonary delivery of PLGA-SV NPs using nebulizer for the treatment of PQ poisoning. However, the efficacy of this formulation in human beings and clinical use needs to be more investigated.

Green preparation, characterization, evaluation of anti-melanogenesis effect and in vitro/in vivo safety profile of kojic acid hydrogel as skin lightener formulation.

The local treatment of kojic acid (KA) as a tyrosinase inhibitor results in inadequate skin absorption and a number of side effects. The current study aims to maximize KA skin delivery. To produce KA-hydrogel, 1% KA was injected into a Chitosan/alginate hydrogel. The impacts of biopolymer proportion on the KA-hydrogel preparations were investigated. Swelling analysis, weight loss analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), UV absorption spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy were used to evaluate the KA-hydrogel. The swelling percentages of KA-hydrogel increased significantly after 4 h. After two weeks, up to 60% of the primary mass of the KA- hydrogel has been removed. By alternation in biopolymer proportion, the drug release profile of KA-hydrogel demonstrated a sustained pattern. According to the skin absorption experiment, KA-hydrogel had higher skin deposition (25.630 ± 3.350%) than KA-plain gel (5.170 ± 0.340%). Moreover, an in vitro cytotoxicity analysis for the modified KA-hydrogel preparations revealed no cytotoxic effects on HFF cell line (90%). Moreover, KA hydrogel had inhibitory effect on melanin synthesis and are comparable with KA. Furthermore, KA-hydrogel had higher inhibitory effect on L-dopa auto oxidation (94.84 ± 2.41%) in comparison KA solution (73.95 ± 3.28%). Also, the dermal irritation study on Wistar rat revealed that the hydrogel constituent used did not irritate the skin. These results revealed that the KA-hydrogel might be employed as KA local administration, thus opening up new prospects for the therapies of hyperpigmentation problems.