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Cancer remains a leading cause of death worldwide, necessitating the development of innovative and more effective treatment strategies. Conventional cancer treatments often suffer from limitations such as systemic toxicity, poor pharmacokinetics, and drug resistance. Recently, there has been growing attention to utilizing natural compounds derived from various sources as possible cancer therapeutics. Natural compounds have demonstrated diverse bioactive properties, including antioxidant, anti-inflammatory, and antitumor effects, making them attractive candidates for cancer treatment. However, their limited solubility and bioavailability present challenges for effective delivery to cancer cells. To overcome these limitations, researchers have turned to nanotechnology-based drug delivery systems. Nanoparticles, with their small size and unique properties, can encapsulate therapeutic agents and offer benefits such as improved solubility, prolonged drug release, enhanced cellular uptake, and targeted delivery. Functionalizing nanoparticles with specific ligands further enhances their precision in recognizing and binding to cancer cells. Combining natural compounds with nanotechnology holds great promise in achieving efficient and safe cancer treatments by enhancing bioavailability, pharmacokinetics, and selectivity toward cancer cells. This review article provides an overview of the advancements in utilizing natural substances and nanotechnology-based drug delivery systems for cancer treatment. It discusses the benefits and drawbacks of various types of nanoparticles, as well as the characteristics of natural compounds that make them appealing for cancer therapy. Additionally, current research on natural substances and nanoparticles in preclinical and clinical settings is highlighted. Finally, the challenges and future perspectives in developing natural compound-nanoparticle-based cancer therapies are discussed., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Cervical cancer (CC) is a major global health problem and leading cause of cancer deaths among women worldwide. Early detection through screening programs has reduced mortality; however, screening compliance remains low. Identifying non-invasive biomarkers through proteomics for diagnosis and monitoring response to treatment could improve patient outcomes. Here we review recent proteomics studies which have uncovered biomarkers and potential drug targets for CC. Additionally, we explore into the role of cervical cancer stem cells and their potential implications in driving CC progression and therapy resistance. Although challenges remain, proteomics has the potential to revolutionize the field of cervical cancer research and improve patient outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jafari, Farahani, Abdollahpour-Alitappeh, Manzari-Tavakoli, Yazdani and Rezaei-Tavirani.)

Objective: High temperatures can trigger cellular oxidative stress and disrupt spermatogenesis, potentially leading to male infertility. We investigated the effects of retinoic acid (RA), chitosan nanoparticles (CHNPs), and retinoic acid loaded with chitosan nanoparticles (RACHNPs) on spermatogenesis in mice induced by scrotal hyperthermia (Hyp)., Methods: Thirty mice (weighing 25 to 30 g) were divided into five experimental groups of six mice each. The groups were as follows: control, Hyp induced by a water bath (43 °C for 30 minutes/day for 5 weeks), Hyp+RA (2 mg/kg/day), Hyp+CHNPs (2 mg/kg/72 hours), and Hyp+RACHNPs (4 mg/kg/72 hours). The mice were treated for 35 days. After the experimental treatments, the animals were euthanized. Sperm samples were collected for analysis of sperm parameters, and blood serum was isolated for testosterone measurement. Testis samples were also collected for histopathology assessment, reactive oxygen species (ROS) evaluation, and RNA extraction, which was done to compare the expression levels of the bax, bcl2, p53, Fas, and FasL genes among groups. Additionally, immunohistochemical staining was performed., Results: Treatment with RACHNPs significantly increased stereological parameters such as testicular volume, seminiferous tubule length, and testicular cell count. Additionally, it increased testosterone concentration and improved sperm parameters. We observed significant decreases in ROS production and caspase-3 immunostaining in the RACHNP group. Moreover, the expression levels of bax, p53, Fas, and FasL significantly decreased in the groups treated with RACHNPs and RA., Conclusion: RACHNPs can be considered a potent antioxidative and antiapoptotic agent for therapeutic strategies in reproductive and regenerative medicine.

Available therapeutic strategies for cancers have developed side effects, resistance, and recurrence that cause lower survival rates. Utilizing targeted drug delivery techniques has opened up new hopes for increasing the efficacy of cancer treatment. The current study aimed to investigate the appropriate condition of primming human amniotic epithelial cells (hAECs) with paclitaxel as a dual therapeutic approach consisting of inherent anticancer features of hAECs and loaded paclitaxel. The effects of paclitaxel on the viability of hAECs were evaluated to find an appropriate loading period. The possible mechanism of hAECs paclitaxel resistance was assessed using verapamil. Afterward, the loading and releasing efficacy of primed hAECs were evaluated by HPLC. The anti-neoplastic effects and apoptosis as possible mechanism of conditioned media of paclitaxel-loaded hAECs were assessed on breast and cervical cancer cell lines. hAECs are highly resistant to cytotoxic effects of paclitaxel in 24 h. Evaluating the role of P-glycoproteins in hAECs resistance showed that they do not participate in hAECs resistance. The HPLC demonstrated that hAECs uptake/release paclitaxel with optimum efficacy in 8000 ng/ml treatment. Assessing the anti-proliferative effect of primed hAECs condition media on cancer cells showed that the secretome induced 3.3- and 4.8-times more potent effects on MCF-7 and HeLa, respectively, and enhanced the apoptosis process. These results suggest that hAECs could possibly be used as a drug delivery system for cancer treatment. Besides, inherent anticancer effects of hAECs were preserved during the modification process. Synergistic anticancer effects of paclitaxel and hAECs can be translated into clinical practice, which would be evaluated in the future studies., (© 2022. The Author(s).)

The bone morphogenetic proteins (BMPs) are a group of potent morphogens which are critical for the patterning, development, and function of the central nervous system. The appropriate function of the BMP pathway depends on its interaction with other signaling pathways involved in neural differentiation, leading to synergistic or antagonistic effects and ultimately favorable biological outcomes. These opposite or cooperative effects are observed when BMP interacts with fibroblast growth factor (FGF), cytokines, Notch, Sonic Hedgehog (Shh), and Wnt pathways to regulate the impact of BMP-induced signaling in neural differentiation. Herein, we review the cross-talk between BMP signaling and the prominent signaling pathways involved in neural differentiation, emphasizing the underlying basic molecular mechanisms regarding the process of neural differentiation. Knowing these cross-talks can help us to develop new approaches in regenerative medicine and stem cell based therapy. Recently, cell therapy has received significant attention as a promising treatment for traumatic or neurodegenerative diseases. Therefore, it is important to know the signaling pathways involved in stem cell differentiation toward neural cells. Our better insight into the cross-talk of signaling pathways during neural development would improve neural differentiation within in vitro tissue engineering approaches and pre-clinical practices and develop futuristic therapeutic strategies for patients with neurological disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Manzari-Tavakoli, Babajani, Farjoo, Hajinasrollah, Bahrami and Niknejad.)

Stem cells are a promising tool for treatment of a variety of degenerative diseases. Human amniotic epithelial stem cells (hAECs) have desirable and unique characteristics that make them a proper candidate for cell therapy. In this study, we have investigated the effects of BMP-4 (bone morphogenetic protein-4) and its inhibition on differentiation of AECs into ectodermal lineages. Analysis of AEC-derived ectodermal lineages (neurons and keratinocytes) was performed by using flow cytometry technique for Map2 and β-tubulin (as neuron markers), Olig2 and MBP (as oligodendrocyte markers), and K14 and K10 (as keratinocyte markers). The results of this study illustrated that noggin (as BMP antagonist), BMP4, and both BMP4 and heparin (together or separately) increased neural and keratinocyte marker expression, respectively. The expression of markers MAP2, olig2, and K14 in hAECs has been significantly decreased 21 days after exposure to differentiation medium (without growth factors) compared with isolation day, which supports the hypothesis that AECs can be dedifferentiated into pluripotent cells. Moreover, activation and inhibition of BMP signaling have no effects on viability of hAECs. The results of this study showed that BMP signaling and its inhibition are the key factors for ectodermal lineage differentiation of amnion-derived stem cells.

The utilization of conductive polymers for fabrication of neural scaffolds have attracted much interest because of providing a microenvironment which can imitate nerve tissues. In this study, polypyrrole (PPy)-alginate (Alg) composites were prepared using different percentages of alginate and pyrrole by oxidative polymerization method using FeCl 3 as an oxidant and electrical conductivity of composites were measured by four probe method. In addition, chitosan-based nanoparticles were synthesized by ionic gelation method and after characterization merged into PPy-Alg composite in order to fabricate a conductive, hydrophilic, processable and stable scaffold. Physiochemical characterization of nanochitosan/PPy-Alg scaffold such as electrical conductivity, porosity, swelling and degradation was investigated. Moreover, cytotoxicity and proliferation were examined by culturing OLN-93 neural and human dermal fibroblasts cells on the Nanochitosan/PPy-Alg scaffold. Due to the high conductivity, the film with ratio 2:10 (PPy-Alg) was recognized more suitable for fabrication of the final scaffold. Results from FT-IR and SEM, evaluation of porosity, swelling and degradation, as well as viability and proliferation of OLN-93 neural and fibroblast cells confirmed cytocompatiblity of the Nanochitosan/PPy-Alg scaffold. Based on the features of the constructed scaffold, Nanochitosan/PPy-Alg scaffold can be a proper candidate for neural tissue engineering.

Context: Otostegia persica Boiss (Lamiaceae) contains antioxidant agents and is used in traditional medicine for treatment of diabetes mellitus complications., Objectives: The acute antihyperglycemic, antilipid peroxidation, and insulin secretory activities of methanol extract of O. persica aerial parts were investigated., Materials and Methods: The extract [200, 300, 400 mg/kg body weight (b.w.)] was given orally to rats and glucose (2 g/kg b.w. orally) was administered 30 min later. Glucose and insulin serum levels were measured before and 30, 60, 120, and 240 min after administration of the test samples in normal and diabetic rats. The in vitro insulin secretory activity of extract was evaluated in C187 pancreatic β-cells and its antilipid peroxidation effect was determined by measuring malondialdehyde (MDA) and glutathione (GSH) levels in rat livers after 240 min. The identification of the major phytoconstituents of the extract was carried out using gas chromatography-mass spectrometry., Results: The extract (300 mg/kg b.w.) significantly decreased the serum glucose level in diabetic rats at 1 h (494 ± 13.4 vs. 426 ± 12.9), 2 h (472.8 ± 17.8 vs. 396 ± 22), and 4 h (438.8 ± 25 vs. 346 ± 19) after treatment. Accordingly, the serum insulin level increased at the same times. The extract significantly increased glucose-induced insulin secretion in C187 β-cells. Moreover, the extract significantly decreased MDA and increased GSH levels in the liver of diabetic rats. Phytochemical analysis revealed thymol as the major phytoconstituent in the extract., Discussion and Conclusion: O. persica shoot extract has antihyperglycemic, antilipid peroxidation, and insulin secretory properties.