Search

Human hepatocellular carcinoma (HCC) has been identified as a significant cause of mortality worldwide. In recent years, extensive research has been conducted to understand the underlying mechanisms of autophagy in the pathogenesis of the disease, with the aim of developing novel therapeutic agents. Targeting autophagy with conventional therapies in invasive HCC has opened up new opportunities for treatment. However, the emergence of resistance and the immunosuppressive tumor environment highlight the need for combination therapy or specific targeting, as well as an efficient drug delivery system to ensure targeted tumor areas receive sufficient doses without affecting normal cells or tissues. In this review, we discuss the findings of several studies that have explored autophagy as a potential therapeutic approach in HCC. We also outline the potential and limitations of standard therapies for autophagy modulation in HCC treatment. Additionally, we discuss how different combination therapies, nano-targeted strategies, and oncolytic virotherapy could enhance autophagy-based HCC treatment in future research., Competing Interests: Declarations. Competing interest: The authors declare no competing interests. Ethics approval and consent to participate: Not applicable., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) poses a significant global health challenge, necessitating innovative therapeutic strategies. MicroRNAs (miRNAs) have emerged as pivotal regulators of HCC pathogenesis, influencing key processes such as self-renewal, angiogenesis, glycolysis, autophagy, and metastasis. This article integrates findings from a comprehensive literature review and bioinformatics analysis to elucidate the role of miRNAs in HCC. We discuss how dysregulation of miRNAs can drive HCC initiation, progression, and metastasis by modulating various signaling pathways and target genes. Moreover, leveraging high-throughput technology and bioinformatics tools, we identify key miRNAs involved in multiple cancer hallmarks, offering insights into potential combinatorial therapeutic strategies. Through our analysis considering p-values and signaling pathways associated with key features, we unveil miRNAs with simultaneous roles across critical cancer characteristics, providing a basis for the development of high-performance biomarkers. The microRNAs, miR-34a-5p, miR-373-3p, miR-21-5p, miR-214-5p, miR-195-5p, miR-139-5p were identified to be shared microRNAs in stemness, angiogenesis, glycolysis, autophagy, EMT, and metastasis of HCC. However, challenges such as miRNA stability and delivery hinder the translation of miRNA-based therapeutics into clinical practice. This review underscores the importance of further research to overcome existing barriers and realize the full potential of miRNA-based interventions for HCC management., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Despite advances in cancer therapies, glioblastoma (GBM) remains the most resistant and recurrent tumor in the central nervous system. GBM tumor microenvironment (TME) is a highly dynamic landscape consistent with alteration in tumor infiltration cells, playing a critical role in tumor progression and invasion. In addition, glioma stem cells (GSCs) with self-renewal capability promote tumor recurrence and induce therapy resistance, which all have complicated eradication of GBM with existing therapies. Oncolytic virotherapy is a promising field of therapy that can kill tumor cells in a targeted manner. Manipulated oncolytic viruses (OVs) improve cancer immunotherapy by directly lysis tumor cells, infiltrating antitumor cells, inducing immunogenic cell death, and sensitizing immune-resistant TME to an immune-responsive hot state. Importantly, OVs can target stemness-driven GBM progression. In this review, we will discuss how OVs as a therapeutic option target GBM, especially the GSC subpopulation, and induce immunogenicity to remodel the TME, which subsequently enhances immunotherapies' efficiency., Competing Interests: Declaration of competing interest The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite the development of a vaccine against cutaneous leishmaniasis in preclinical and clinical studies, we still do not have a safe and effective vaccine for human use. Given this situation, the search for a new prophylactic alternative to control leishmaniasis should be a global priority. A first-generation vaccine strategy-leishmanization, in which live Leishmania major parasites are inoculated into the skin to protect against reinfection, is taking advantage of this situation. Live attenuated Leishmania vaccine candidates are promising alternatives due to their robust protective immune responses. Importantly, they do not cause disease and could provide long-term protection following challenges with a virulent strain. In addition to physical and chemical methods, genetic tools, including the Cre- loxP system, have enabled the selection of safer null mutant live attenuated Leishmania parasites obtained by gene disruption. This was followed by the discovery and introduction of CRISPR/Cas-based gene editing tools, which can be easily and precisely used to modify genes. Here, we briefly review the immunopathology of L. major parasites and then present the classical methods and their limitations for the production of live attenuated vaccines. We then discuss the potential of current genetic engineering tools to generate live attenuated vaccine strains by targeting key genes involved in L. major pathogenesis and then discuss their discovery and implications for immune responses to control leishmaniasis., 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 Rooholamini, Dianat-Moghadam, Esmaeilifallah and Khanahmad.)

Background: The antiviral properties of metal nanoparticles against various viruses, including those resistant to drugs, are currently a subject of intensive research. Recently, the green synthesis of nanoparticles and their anti-viral function have attracted a lot of attention. Previous studies have shown promising results in the use of Arabic gum for the green synthesis of nanoparticles with strong antiviral properties. In this study we aimed to investigate the antiviral effects of MnO 2 nanoparticles (MnO 2 -NPs) synthesized using Arabic gum, particularly against the influenza virus., Methods: Arabic gum was used as a natural polymer to extract and synthesize MnO 2 -NPs using a green chemistry approach. The synthesized MnO 2 -NPs were characterized using SEM and TEM. To evaluate virus titration, cytotoxicity, and antiviral activity, TCID50, MTT, and Hemagglutination assay (HA) were performed, respectively. Molecular docking studies were also performed to investigate the potential antiviral activity of the synthesized MnO 2 -NPs against the influenza virus. The molecular docking was carried out using AutoDock Vina software followed by an analysis with VMD software to investigate the interaction between Arabic gum and the hemagglutinin protein., Results: Simultaneous combination treatment with the green-synthesized MnO 2 -NPs resulted in a 3.5 log HA decrement and 69.7% cellular protection, which demonstrated the most significant difference in cellular protection compared to the virus control group (p-value < 0.01). The docking results showed that binding affinities were between - 3.3 and - 5.8 kcal/mole relating with the interaction between target with MnO 2 and beta-D-galactopyranuronic acid, respectively., Conclusion: The results of the study indicated that the MnO 2 -NPs synthesized with Arabic gum had significant antiviral effects against the influenza virus, highlighting their potential as a natural and effective treatment for inhibition of respiratory infections., (© 2024. The Author(s).)

Unlike MCF-7 cells, MDA-MB-231 cells are unresponsive to hormone therapy and often show resistance to chemotherapy and radiotherapy. Here, the antiproliferative effect of biocompatible montmorillonite (Mt) nanosheets on MDA-MB-231 and MCF-7 human breast cancer cells was evaluated by MTT assay, flow cytometry, and qRT-PCR. The results showed that the Mt IC 50 for MDA-MB-231 and MCF-7 cells in a fetal bovine serum (FBS)-free medium was ~50 and ~200 µg/mL, and in 10% FBS medium ~400 and ~2000 µg/mL, respectively. Mt caused apoptosis in both cells by regulating related genes including Cas-3 , P53 , and P62 in MDA-MB-231 cells and Bcl-2 , Cas-8 , Cas-9 , P53 , and P62 in MCF-7 cells. Also, Mt arrested MCF-7 cells in the G0/G1 phase by altering Cyclin-D1 and P21 expression, and caused sub-G1 arrest and necrosis in both cells, possibly through damaging the mitochondria. However, fewer gene expression changes and more sub-G1 arrest and necrosis were observed in MDA-MB-231 cells, confirming the higher vulnerability of MDA-MB-231 cells to Mt. Furthermore, MDA-MB-231 cells appeared to be much more vulnerable to Mt compared to other cell types, including normal lung fibroblast (MRC-5), colon cancer (HT-29), and liver cancer (HepG2) cells. The higher vulnerability of MDA-MB-231 cells to Mt was inferred to be due to their higher proliferation rate. Notably, Mt cytotoxicity was highly dependent on both the Mt concentration and serum level, which favors Mt for the local treatment of MDA-MB-231 cells. Based on these results, Mt can be considered as an antiproliferative nanoagent against MDA-MB-231 cells and may be useful in the development of local nanoparticle-based therapies.

M13 phages possessing filamentous phage genomes offer the benefits of selective display of molecular moieties and delivery of therapeutic agent payloads with a tolerable safety profile. M13 phage-displayed technology for resembling antigen portions led to the discovery of mimetic epitopes that applied to antibody-based therapy and could be useful in the design of anticancer vaccines. To date, the excremental experiences have engaged the M13 phage in the development of innovative biosensors for detecting biospecies, biomolecules, and human cells with an acceptable limit of detection. Addressing the emergence of antibiotic-resistant bacteria, M13 phages are potent for packaging the programmed gene editing tools, such as CRISPR/Cas, to target multiple antimicrobial genes. Moreover, their display potential in combination with nanoparticles inspires new approaches for engineering targeted theragnostic platforms targeting multiple cellular biomarkers in vivo. In this review, we present the available data on optimizing the use of bacteriophages with a focus on the to date experiences with M13 phages, either as monoagent or as part of combination regimens in the practices of biosensors, vaccines, bactericidal, modeling of specific antigen epitopes, and phage-guided nanoparticles for drug delivery systems. Despite increasing research interest, a deep understanding of the underlying biological and genetic behaviors of M13 phages is needed to enable the full potential of these bioagents in biomedicine, as discussed here. We also discuss some of the challenges that have thus far limited the development and practical marketing of M13 phages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Angiogenesis is a hallmark of cancer biology, and neoadjuvant therapies targeting either tumor vasculature or VEGF signaling have been developed to treat solid malignant tumors. However, these therapies induce complete vascular depletion leading to hypoxic niche, drug resistance, and tumor recurrence rate or leading to impaired delivery of chemo drugs and immune cell infiltration at the tumor site. Achieving a balance between oxygenation and tumor growth inhibition requires determining vascular normalization after treatment with a low dose of antiangiogenic agents. However, monotherapy within the approved antiangiogenic agents' benefits only some tumors and their efficacy improvement could be achieved using immunotherapy and emerging nanocarriers as a clinical tool to optimize subsequent therapeutic regimens and reduce the need for a high dosage of chemo agents. More importantly, combined immunotherapies and nano-based delivery systems can prolong the normalization window while providing the advantages to address the current treatment challenges within antiangiogenic agents. This review summarizes the approved therapies targeting tumor angiogenesis, highlights the challenges and limitations of current therapies, and discusses how vascular normalization, immunotherapies, and nanomedicine could introduce the theranostic potentials to improve tumor management in future clinical settings., 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 © 2023 Dianat-Moghadam, Nedaeinia, Keshavarz, Azizi, Kazemi and Salehi.)

Many problems related to disorders and defects of bone tissue caused by aging, diseases, and injuries have been solved by the multidisciplinary research field of regenerative medicine and tissue engineering. Numerous sciences, especially nanotechnology, along with tissue engineering, have greatly contributed to the repair and regeneration of tissues. Various studies have shown that the presence of magnetic nanoparticles (MNPs) in the structure of composite scaffolds increases their healing effect on bone defects. In addition, the induction of osteogenic differentiation of mesenchymal stem cells (MSCs) in the presence of these nanoparticles has been investigated and confirmed by various studies. Therefore, in the present article, the types of MNPs, their special properties, and their application in the healing of damaged bone tissue have been reviewed. Also, the molecular effects of MNPs on cell behavior, especially in osteogenesis, have been discussed. Finally, the present article includes the potential applications of MNP-containing nanocomposite scaffolds in bone lesions and injuries. In summary, this review article highlights nanocomposite scaffolds containing MNPs as a solution for treating bone defects in tissue engineering and regenerative medicine., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Glioblastoma multiforme (GBM) is one of the most aggressive brain and spinal cord tumors. Despite the significant development in application of antitumor drugs, no significant increases have been observed in the survival rates of patients with GBM, as GBM cells acquire resistance to conventional anticancer therapeutic agents. Multiple studies have revealed that PI3K/Akt, MAPK, Nanog, STAT 3, and Wnt signaling pathways are involved in GBM progression and invasion. Besides, biological processes such as anti-apoptosis, autophagy, angiogenesis, and stemness promote GBM malignancy. Resveratrol (RESV) is a non-flavonoid polyphenol with high antitumor activity, the potential of which, regulating signaling pathways involved in cancer malignancy, have been demonstrated by many studies. Herein, we present the potential of RESV in both single and combination therapy- targeting various signaling pathways- which induce apoptotic cell death, re-sensitize cancer cells to radiotherapy, and induce chemo-sensitizing effects to eventually inhibit GBM progression., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Reprogrammed metabolism and active stemness contribute to cancer stem cells' (CSCs) survival and tumorigenesis. LXR signaling regulates the metabolism of different cancers. A selective LXR inhibitor, SR9243 (SR), can target and eradicate non-CSC tumor cells. CD133 is a stem marker in solid tumors-associated CSCs within the active lipogenesis, and anti-CD133 mAb targeting liposomal drug delivery systems expected to increase drug internalization and improve the therapeutic efficacy of poor-in water solubility drugs, e, g., SR. In this study, anti-CD133 mAbs-targeted Immunoliposomes (ILipo) were developed for specific delivery of SR into MACS-enriched CD133 + CSCs and induce their functional effects. Results have shown that ILipo having an average size of 64.79 nm can encapsulate SR in maximum proportion, and cell association studies have shown cationic ILipo and targeting CD133 provide the CSCs binding. Also, FCM analysis of RhoB has demonstrated that the ILipo uptake was higher in CD133 + CSCs than in the non-targeted liposomes. ILipo-SR was significantly more toxic in CD133 + CSCs compared to the free SR and non-targeted ones. More efficient than Lipo-SR, ILipo-SR improved the reduction of clonogenicity, stemness, and lipogenesis in CD133 + CSCs in vitro, boosted ROS generation, and induced apoptosis. Our study revealed the dual targeting of CD133 and LXR appears to be a promising strategy for targeting CD133 + CSCs-presenting dynamic metabolism and self-renewal potentials., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intra-tumoral immune cells promote the stemness of cancer stem cells (CSCs) in the tumor microenvironment (TME). CSCs promote tumor progression, relapse, and resistance to immunotherapy. Cancer stemness induces the expression of neoantigens and neo-properties in CSCs, creating an opportunity for targeted immunotherapies. Isolation of stem-like T cells or retaining stemness in T clonotypes strategies produces exhaustion-resistance T cells with superior re-expansion capacity and long-lasting responses after adoptive cell therapies. Stem cells-derived NK cells may be the next generation of NK cell products for immunotherapy. Here, we have reviewed mechanisms by which stemness factors modulated the immunoediting of the TME and summarized the potentials of CSCs in the development of immunotherapy regimens, including CAR-T cells, CAR-NK cells, cancer vaccines, and monoclonal antibodies. We have discussed the natural or genetically engineered stem-like T cells and stem cell-derived NK cells with increased cytotoxicity to tumor cells. Finally, we have provided a perspective on approaches that may improve the therapeutic efficacy of these novel adoptive cell-based products in targeting immunosuppressive TME., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Colorectal cancer (CRC) is one of the most frequent cancers leading to death worldwide. Different signaling pathways such as the canonical Wnt signaling pathway have many effects on the development of CRC. MicroRNAs are small non-coding RNAs and different evidence represent their importance in the development of cancer via regulating the expression of their target genes. miRNAs can affect CRC progression as oncogenes or tumor suppressors. Dysregulation in miRNA expression can occur for various reasons, causes different abnormalities in the Wnt signaling pathway, and contributes to CRC development. Identifying the exact interactions between microRNAs and mRNAs or other non-coding RNAs assists in designing effective therapeutic, diagnostic, and prognostic approaches. In this review, we aim to focus on microRNAs that regulate CRC through modulating the Wnt pathway and then present the perspective outlook on the implication of miRNA in liquid biopsy for the management of patients with CRC., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recent studies demonstrated that the speed of synthesis, biocompatibility, and antimicrobial activity of gold (Au) and silver (Ag) metals is enhanced when biosynthesized in nano-sized particles. In the present study, Au- and Ag-based nanoparticles (NPs) were synthesized via a biological process using aqueous Ginger root extract and characterized by various spectroscopic methods. The NPs have hexagonal and spherical shapes. The average particle size for Au and Ag NPs was 20 and 15 nm, respectively. The dynamic light scattering (DLS) technique has shown that the zeta potential values of synthesized NPs were 4.8 and - 7.11 mv, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis of Ginger root extract revealed 25 compounds. The synthesized NPs showed significant activity against Staphylococcus aureus and Escherichia (E). coli in vitro, with IC 50 and IC 90 values for Au and Ag NPs, respectively, noted to be 7.5 and 7.3 µg/ml and 15 and 15.2 µg/ml for both bacterial strains. The protein leakage level was tremendous and morphological changes occurred in bacteria treated with biosynthesized NPs. These results suggest that the biosynthesized metallic NPs have the suitable potential for application as antibacterial agents with enhanced activities., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Plant virus nanoparticles (PVNPs) have inherent immune stimulatory ability, and have been investigated as immune adjuvants to stimulate an anti-tumor immune response. The combination of immune stimulation, nanoparticle structure and the ability to deliver other therapeutic molecules provides a flexible platform for cancer immunotherapy. Researching multifunctional PVNPs and their modification will generate novel reagents for cancer immunotherapy. Here we review the properties of PVNPs, and their potential for clinical utilization to activate anti-tumor innate and lymphoid immune responses. PVNPs have potential utility for cancer immunotherapy as vaccine adjuvant, and delivery systems for other reagents as mono immunotherapy or combined with other immunotherapies. This review outlines the potential and challenges in developing PVNPs as cancer immunotherapy reagents., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Breast cancer treatment using plant-virus-based nanoparticles (PVNPs) has achieved considerable success in preclinical studies. PVNP-based breast cancer therapies include non-targeted and targeted nanoplatforms for delivery of anticancer therapeutic chemo and immune agents and cancer vaccines for activation of local and systemic antitumor immunity. Interestingly, PVNP platforms combined with other tumor immunotherapeutic options and other modalities of oncotherapy can improve tumor efficacy treatment. These applications can be achieved by encapsulation of a wide range of active ingredients and conjugating ligands for targeting immune and tumor cells. This review presents the current breast cancer treatments based on PVNP platforms.

Objectives: This investigation aims to evaluate the association between the concentration of cell-free DNA (cfDNA) in the spent culture medium (SCM) with implantation rate and the maternal immune system in the invitro fertilization (IVF). In this study, 30 embryos were cultured and scored according to Gardner's criteria. SCM was gathered on day five from every embryo to analyze the quantity of cfDNA. The real-time PCR technique evaluated the expression level of transcription factors, including Foxp3, RORγt, GATA3, and T-bet. The percentage of Th1, Th2, Th17, Treg, NK cells, and NK cells cytotoxicity was evaluated by flow cytometry., Results: The concentration of cfDNA in the β-HCG (-), β-HCG ( +), and ongoing pregnancy groups were 20.70 ± 9.224 ng/µL, 27.97 ± 7.990 ng/µL, and 28.91 ± 8.566 ng/µL, respectively. The ratio of Th1/Th2 and Th17/Treg reduced significantly in pregnant women, as well as the level of NK cells and NK cytotoxicity cells fell dramatically in the ongoing pregnancy group. The expression level of RORγt and T-bet declined while the expression level of Foxp3 and GATA3 increased considerably in pregnant mothers. Our investigation revealed that the concentration level of cfDNA in SCM could not be associated with implantation rate, prediction of ongoing pregnancy, and maternal immune system., (© 2022. The Author(s).)

Oncolytic viruses (OVs) harness the hallmarks of tumor cells and cancer-related immune responses for the lysis of malignant cells, modulation of the tumor microenvironment, and exertion of vaccine-like activities. However, efficient clinical exploitation of these potent therapeutic modules requires their systematic administration, especially against metastatic and solid tumors. Therefore, developing methods for shielding a virus from the neutralizing environment of the bloodstream while departing toward tumor sites is a must. This paper reports the latest advancements in the employment of chemical and biological compounds aimed at safe and efficient delivery of OVs to target tissues or tumor deposits within the host., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Exploration of tumor immunity leads to the development of immune checkpoint inhibitors and cell-based immunotherapies which improve the clinical outcomes in several tumor types. However, the poor clinical efficacy of these treatments observed for other tumors could be attributed to the inherent complex tumor microenvironment (TME), cellular heterogeneity, and stemness driven by cancer stem cells (CSCs). CSC-specific characteristics provide the bulk tumor surveillance and resistance to entire eradication upon conventional therapies. CSCs-immune cells crosstalk creates an immunosuppressive TME that reshapes the stemness in tumor cells, resulting in tumor formation and progression. Thus, identifying the immunological features of CSCs could introduce the therapeutic targets with powerful antitumor responses. In this review, we summarized the role of immune cells providing CSCs to evade tumor immunity, and then discussed the intrinsic mechanisms represented by CSCs to promote tumors' resistance to immunotherapies. Then, we outlined potent immunotherapeutic interventions followed by a perspective outlook on the use of nanomedicine-based drug delivery systems for controlled modulation of the immune system., (© 2022. The Author(s).)

Background: The bone tissue engineering (BTE) approach has been introduced as an alternative to conventional treatments for large non-healing bone defects. Magnetism promotes stem cells' adherence to biocompatible scaffolds toward osteoblast differentiation. Furthermore, osteogenic differentiation media are expensive and any changes in its composition affect stem cells differentiation. Moreover, media growth factors possess a short half-life resulting in the rapid loss of their functions in vivo. With the above in mind, we fabricated a multilayered nanocomposite scaffold containing the wild type of Type I collagen (Col I) with endogenous magnetic property to promote osteogenesis in rat ADSCs with the minimum requirement of osteogenic differentiation medium., Methods: Fe 3 O 4 NPs were synthesized by co-precipitation method and characterized using SEM, VSM, and FTIR. Then, a PCL/Col I nanocomposite scaffold entrapping Fe 3 O 4 NPs was fabricated by electrospinning and characterized using SEM, TEM, AFM, VSM, Contact Angle, tensile stretching, and FTIR. ADSCs were isolated from rat adipose tissue and identified by flow cytometry. ADSCs were loaded onto PCL/Col I and PCL/Col I/Fe 3 O 4 -scaffolds for 1-3 weeks with/without osteogenic media conditions. The cell viability, cell adhesion, and osteogenic differentiation were evaluated using MTT assay, SEM, DAPI staining, ALP/ARS staining, RT-PCR, and western blotting, respectively., Results: SEM, VSM, and FTIR results indicated that Fe 3 O 4 was synthesized in nano-sized (15-30 nm) particles with spherical-shaped morphology and superparamagnetic properties with approved chemical structure as FTIR revealed. According to SEM images, the fabricated magnetic scaffolds consisted of nanofiber (500-700 nm). TEM images have shown the Fe 3 O 4 NPs entrapped in the scaffold's fiber without bead formation. FTIR spectra analysis confirmed the maintenance of the natural structure of Col I, PCL, and Fe 3 O 4 upon electrospinning. AFM data have shown that MNPs incorporation introduced stripe-like topography to nanofibers, while the depth of the grooves has decreased from 800 to 500 nm. Flow cytometry confirmed the phenotype of ADSCs according to their surface markers (i.e., CD29 and CD105). Additionally, Fe 3 O 4 NP improved nanocomposite scaffold strength, wettability, porosity, biocompatibility and also facilitates the ALP activity, calcium-mineralization. Finally, magnetic nanocomposite scaffolds upregulated osteogenic-related genes or proteins' expression (e.g., Col I, Runx2, OCN, ON, BMP2) in seeded ADSCs with/without osteo-differentiation media conditions., Conclusions: Together, these results indicate that Fe 3 O 4 NPs within the natural structure of Col I increase osteogenic differentiation in osteogenic cues-free media conditions. This effect could be translated in vivo toward bone defects healing. These findings support the use of natural ECM materials alongside magnetic particles as composite scaffolds to achieve their full therapeutic potential in BTE treatments., (© 2022. The Author(s).)

Various biopsy and sampling methods are used for preimplantation genetic diagnosis (PGD) of embryo. This method benefits blastomer/trophectoderm biopsy to improve the clinical outcome of in vitro fertilization (IVF). However, all of these procedures are invasive and have adverse effects on embryo development. Additionally, these procedures require expensive equipment and well-experienced technicians. Regarding these limitations, designing non-invasive methods is necessary. One of the recently proposed non-invasive and applicable methods is cell free DNA (cfDNA) molecule evaluation that have opened up exciting opportunities in the molecular diagnosis of embryo and fetus chromosomal aneuploidy. cfDNA is present in body fluids; especially blood, follicular fluid, amniotic fluid, spent embryo culture medium (SCM) and blastocoel fluid. Overall, this review highlights the cfDNA biomarker might constitute a supplemental tool for improving IVF and pregnancy outcomes, female infertility management. However, the successful application of cfDNA demands an understanding of its biological properties, kinetics, time of collection, high sensitivity and specificity cfDNA detection methods, and their limitation and challenges in the clinical settings. In this review we also describe ethical aspects of cfDNA testing., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Understanding the molecular mechanisms of cancer biology introduces targeted therapy as a complementary method along with other conventional therapies. Recombinant immunotoxins are tumor specific antibodies that their recognizing fragment is utilized for delivering modified toxins into tumor cells. These molecules have been considered as a targeted strategy in the treatment of human cancers. HER2 tumor biomarker is a transmembrane tyrosine kinase receptor that can be used for targeted therapies in the forms of anti-HER2 monoclonal antibodies, antibody-drug conjugates and immunotoxins. There have been many studies on HER2-based immunotoxins in recent years, however, little progress has been made in the clinical field which demanded more improvements. Here, we summarized the HER2 signaling and it's targeting using immunotherapeutic agents in human cancers. Then, we specifically reviewed anti-HER2 immunotoxins, and their strengths and drawbacks to highlight their promising clinical impact., (© 2021. The Author(s).)

Background: The expansion and metastasis of colorectal cancers are closely associated with the dynamic growth of cancer stem cells (CSCs). This study aimed to explore the possible effect of LXR (a regulator of glycolysis and lipid hemostasis) in the tumorgenicity of human colorectal CD133 cells., Methods: Human HT-29 CD133 + cells were enriched by MACS and incubated with LXR agonist (T0901317) and antagonist (SR9243) for 72 h. Cell survival was evaluated using MTT assay and flow cytometric analysis of Annexin-V. The proliferation rate was measured by monitoring Ki-67 positive cells using IF imaging. The modulation of LXR was studied by monitoring the activity of all factors related to ABC transporters using real-time PCR assay and western blotting. Protein levels of metabolic enzymes such as PFKFB3, GSK3β, FASN, and SCD were also investigated upon treatment of CSCs with LXR modulators. The migration of CSCs was monitored after being exposed to LXR agonist using scratch and Transwell insert assays. The efflux capacity was measured using hypo-osmotic conditions. The intracellular content of reactive oxygen species was studied by DCFH-DA staining., Results: Data showed incubation of CSCs with T0901317 and SR9243 reduced the viability of CD133 cells in a dose-dependent manner compared to the control group. The activation of LXR up-regulated the expression and protein levels of ABC transporters (ABCA1, ABCG5, and ABCG8) compared to the non-treated cells (p < 0.05). Despite these effects, LXR activation suppressed the proliferation, clonogenicity, and migration of CD133 cells, and increased hypo-osmotic fragility (p < 0.05). We also showed that SR9243 inhibited the proliferation and clonogenicity of CD133 cells through down-regulating metabolic enzymes PFKFB3, GSK3β, FASN, and SCD as compared with the control cells (p < 0.05). Intracellular ROS levels were increased after the inhibition of LXR by SR9243 (p < 0.05). Calling attention, both T0901317 and SR9243 compounds induced apoptotic changes in cancer stem cells (p < 0.05)., Conclusions: The regulation of LXR activity can be considered as a selective targeting of survival, metabolism, and migration in CSCs to control the tumorigenesis and metastasis in patients with advanced colorectal cancers.

Metastasis is the major cause of cancer-related deaths. Invasive primary cancers often metastasize after circulating tumor cells (CTCs) enter the bloodstream or lymph node to colonize adjacent tissue or distant anatomical locations. CTCs interact with immune cells and metastatic microenvironments, survival signaling, and chemotherapeutic resistance. Among immune cells, natural killer (NK) cells can, directly and indirectly, interact with CTCs to control cancer metastasis. Understanding the molecular mechanisms that drive NK cells mediated recognition and elimination of CTCs may pave the way for a new generation of anti-CTC molecularly targeted immunotherapies. In this review, we will discuss i) the role of CTCs in metastases, ii) CTCs in the context of the tumor microenvironment, iii) CTCs immune escape, and finally, iv) the potentials of NK cell-based therapies alone, or in combination with nanomedicine for targeted-immunotherapies of metastatic diseases., (Copyright © 2020. Published by Elsevier B.V.)

Although considerable efforts have been conducted to diagnose, improve, and treat cancer in the past few decades, existing therapeutic options are insufficient, as mortality and morbidity rates remain high. Perhaps the best hope for substantial improvement lies in early detection. Recent advances in nanotechnology are expected to increase the current understanding of tumor biology, and will allow nanomaterials to be used for targeting and imaging both in vitro and in vivo experimental models. Owing to their intrinsic physicochemical characteristics, nanostructures (NSs) are valuable tools that have received much attention in nanoimaging. Consequently, rationally designed NSs have been successfully employed in cancer imaging for targeting cancer-specific or cancer-associated molecules and pathways. This review categorizes imaging and targeting approaches according to cancer type, and also highlights some new safe approaches involving membrane-coated nanoparticles, tumor cell-derived extracellular vesicles, circulating tumor cells, cell-free DNAs, and cancer stem cells in the hope of developing more precise targeting and multifunctional nanotechnology-based imaging probes in the future., Competing Interests: Conflict of Interest MRH Scientific Advisory Boards: Transdermal Cap Inc, Cleveland, OH; BeWell Global Inc, Wan Chai, Hong Kong; Hologenix Inc. Santa Monica, CA; LumiThera Inc, Poulsbo, WA; Vielight, Toronto, Canada; Quantum Dynamics LLC, Cambridge, MA; Global Photon Inc, Bee Cave, TX; Medical Coherence, Boston MA; NeuroThera, Newark DE; JOOVV Inc, Minneapolis-St. Paul MN; AIRx Medical, Pleasanton CA; FIR Industries, Inc. Ramsey, NJ; UVLRx Therapeutics, Oldsmar, FL; Ultralux UV Inc, Lansing MI.

Background: Human papillomavirus (HPV)-associated malignancy remain a main cause of cancer in men and women. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor., Methods: For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune responses, caspase-3 and -9 expression, and myeloid and myeloid-derived suppressor cells (MDSCs) by histological and immunohistochemical studies in the tumor microenvironment (TME)., Results: Our findings proved that MSCs possess both migratory capacity and tumor tropism toward transplanted tumor tissue after peritumoral administration. Tumor therapy experiments indicated that oncolytic NDV delivered by MSCs-engineered system significantly reduces tumor growth, which is associated with the enhancement of E7-specific lymphocyte proliferation, CD8+ T cell cytolysis responses, and splenic IFN-γ, IL-4 and IL-12 responses compared with control groups. Moreover, the treatment upregulated the concentration of apoptotic proteins (caspase 9) and increased infiltration of tumor microenvironment with CD11b + myeloid and Gr1 + MDSCs cells., Conclusions: Our data suggest MSCs carrying oncolytic NDV as a potentially effective strategy for cancer immunotherapy through inducing splenic Th1 immune responses and apoptosis in the tumor microenvironment.

TNF-related apoptosis-inducing ligand (TRAIL) selectively induces the apoptosis pathway in tumor cells leading to tumor cell death. Because TRAIL induction can kill tumor cells, cancer researchers have developed many agents to target TRAIL and some of these agents have entered clinical trials in oncology. Unfortunately, these trials have failed for many reasons, including drug resistance, off-target toxicities, short half-life, and specifically in gene therapy due to the limited uptake of TRAIL genes by cancer cells. To address these drawbacks, translational researchers have utilized drug delivery platforms. Although, these platforms can improve TRAIL-based therapies, they are unable to sufficiently translate the full potential of TRAIL-targeting to clinically viable products. Herein, we first summarize the complex biology of TRAIL signaling, including TRAILs cross-talk with other signaling pathways and immune cells. Next, we focus on known resistant mechanisms to TRAIL-based therapies. Then, we discuss how nano-formulation has the potential to enhance the therapeutic efficacy of TRAIL protein. Finally, we specify strategies with the potential to overcome the challenges that cannot be addressed via nanotechnology alone, including the alternative methods of TRAIL-expressing circulating cells, tumor-targeting bacteria, viruses, and exosomes., Competing Interests: Declaration of Competing Interest Dr. Zohreh Amoozgar is one of the patent holders (US Patent Numbers 15,311,339 and 15,503,766) for coated/protein-based particles for drug delivery. The remaining authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Metastases and cancer recurrence are the main causes of cancer death. Circulating Tumor Cells (CTCs) and disseminated tumor cells are the drivers of cancer cell dissemination. The assessment of CTCs' clinical role in early metastasis prediction, diagnosis, and treatment requires more information about their biology, their roles in cancer dormancy, and immune evasion as well as in therapy resistance. Indeed, CTC functional and biochemical phenotypes have been only partially characterized using murine metastasis models and liquid biopsy in human patients. CTC detection, characterization, and enumeration represent a promising tool for tailoring the management of each patient with cancer. The comprehensive understanding of CTCs will provide more opportunities to determine their clinical utility. This review provides much-needed insights into this dynamic field of translational cancer research.

Thanks to the synthetic biology, the laborious and restrictive procedure for producing a target protein in living microorganisms by biotechnological approaches can now experience a robust, pliant yet efficient alternative. The new system combined with lab-on-chip microfluidic devices and nanotechnology offers a tremendous potential envisioning novel cell-free formats such as DNA brushes, hydrogels, vesicular particles, droplets, as well as solid surfaces. Acting as robust microreactors/microcompartments/minimal cells, the new platforms can be tuned to perform various tasks in a parallel and integrated manner encompassing gene expression, protein synthesis, purification, detection, and finally enabling cell-cell signaling to bring a collective cell behavior, such as directing differentiation process, characteristics of higher order entities, and beyond. In this review, we issue an update on recent cell-free protein synthesis (CFPS) formats. Furthermore, the latest advances and applications of CFPS for synthetic biology and biotechnology are highlighted. In the end, contemporary challenges and future opportunities of CFPS systems are discussed., (© 2019 Wiley Periodicals, Inc.)

Although Oncolytic viruses have been regarded as a promising tool for targeted therapy of cancer, accomplishing high efficacy and specificity with this strategy is challenging. Oncolytic virotherapy is one of the novel therapeutic methods recently used for the therapy of human malignancies. Cervical cancer is on the major public health problem and the second most common cause of cancer death among females in less developed countries. The aim of this study was mainly to determine the apoptosis effect of oncolytic Newcastle disease virus (NDV) in TC-1 cell line. In the current study, the oncolytic NDV, vaccine strain LaSota, was used to infect murine TC-1 cells of human papillomavirus (HPV)-associated carcinoma which expressing human papillomavirus 16 (HPV-16) E6/E7 antigens in vitro. The effectiveness of NDV for cervical cancer cell line was investigated by evaluating the antitumor activity of oncolytic NDV and the involved mechanisms. Antitumor activities of oncolytic NDV were assessed by cell proliferation (MTT) and lactate dehydrogenase (LDH) release analysis. In addition, molecular changes of early stage of apoptosis and the role of reactive oxygen species (ROS) were analyzed by flow cytometry and Western Blot in NDV-treated TC-1 cells. The results showed that NDV treatment significantly decreased the viability of a TC-1 cell line and suppressed the growth by inducing apoptotic cell death. In addition, we demonstrated that NDV-induced apoptosis of TC-1 cells is mediated by ROS production. In summary, our findings suggest that oncolytic NDV is a possible therapeutic candidate as a selective antitumor agent for the treatment of cervical cancer., (© 2019 Production and hosting by Elsevier B.V. on behalf of King Saud University.)

Fibroblast growth factors (FGFs) are pleiotropic molecules exerting autocrine, intracrine and paracrine functions via activating four tyrosine kinase FGF receptors (FGFR), which further trigger a variety of cellular processes including angiogenesis, evasion from apoptosis, bone formation, embryogenesis, wound repair and homeostasis. Four major mechanisms including angiogenesis, inflammation, cell proliferation, and metastasis are active in FGF/FGFR-driven tumors. Furthermore, gain-of-function or loss-of-function in FGFRs1-4 which is due to amplification, fusions, mutations, and changes in tumor-stromal cells interactions, is associated with the development and progression of cancer. Although, the developed small molecule or antibodies targeting FGFR signaling offer immense potential for cancer therapy, emergence of drug resistance, activation of compensatory pathways and systemic toxicity of modulators are bottlenecks in clinical application of anti-FGFRs. In this review, we present FGF/FGFR structure and the mechanisms of its function, as well as cross-talks with other nodes and/or signaling pathways. We describe deregulation of FGF/FGFR-related mechanisms in human disease and tumor progression leading to the presentation of emerging therapeutic approaches, resistance to FGFR targeting, and clinical potentials of individual FGF family in several human cancers. Additionally, the underlying biological mechanisms of FGF/FGFR signaling, besides several attempts to develop predictive biomarkers and combination therapies for different cancers have been explored., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

It is verified that failure in cancer therapy by conventional chemotherapeutic agents arise from cancer heterogeneity. That, a small subpopulation of cancer cells known as "cancer stem cells" (CSCs) are shown to be responsible for deriving clonal heterogeneity/diversity in tumors, which render them resistant to conventional treatment regimes. So far, efficient targeted cancer therapy by nanotechnology-based drug delivery approaches is well established. Among various introduced nanocarriers, the non-toxic nature and biocompatibility of liposome make it highly desirable for human studies. In addition, liposomal nanocarriers can be used to protect entrapped therapeutic agents against chemical and biological degradation, improve solubility of the encapsulated drugs, provide sustained drug release, extend in vivo half-life, reduce side effects, improve drug pharmacokinetic and pharmacodynamic profiles, reduce drug dosage and administration frequency. Further, multifunctional liposomes can be envisioned that are simultaneously loaded with different theranostics and chemically-modified with different tumor-specific surface ligands for targeted therapy. Such versatile nanocarrier can influence the physicochemical characteristics, immunological mechanisms, and uptake mechanisms following systemic delivery. Other strategies to improve tumor-specific tropism include delivery systems involving immune cells or their modulators. Here, we describe mechanisms by which CSC can promote drug resistance to impair the efficacy of cancer therapies. Then, we summarize the implication of each of these mechanisms as potential therapeutics ways to overcome the therapeutically-resistant CSCs. Further, we discuss the status, therapeutic potential and prospect of different liposomal drug delivery systems in overcoming CSC drug resistance in the clinic., (Copyright © 2018. Published by Elsevier B.V.)

Influenza A virus is known worldwide as a threat associated with human and livestock diseases. Hence, identification of physiological and molecular aspects of influenza A could contribute to better design of therapeutic approaches for reducing adverse effects associated with disease caused by this virus. miRNAs are epigenetic regulators playing important roles in many pathological processes that help in progression of influenza A. Besides miRNAs, exosomes have ememrged as other effective players in influenza A pathogenesis. Exosomes exert their effects via targeting their cargos (e.g., DNAs, mRNA, miRNAs and proteins) to recipient cells. Here, we summarized various roles of miRNAs and exosomes in influenza A pathogenesis. Moreover, we highlighted therapeutic applications of miRNAs and exosomes in influenza.

Natural killer (NK) cells are key players of the innate immune system. NK cells provide protection against infectious pathogens and malignancies in cell. This characteristic may be attributable to their intrinsic diverse potentialities and also their cooperation with adaptive immune lymphocytes, known as B and T cells. The growth, recurrence, and metastasis of cancer cells, and the failure of cytoreductive therapies against cancer cells are due to the small population of intratumor stem-like cells, called cancer stem cells (CSCs). Furthermore, NK cells can efficiently eradicate heterogeneous tumor cells after a long-term treatment. Therefore, NK cell-based therapy is a promising strategy to target and break CSC-associated resistance to anticancer drugs treatment. In this review, we have presented an overview of the emerging knowledge of the characteristics, diversities, and mechanism-driven immune surveillance of human NK cells and advances in NK cell-based immunotherapies. Finally, we will discuss how these cells can be applied to introduce the next generation of vaccine- and immune-based approaches to prevent drug resistance., (© 2018 Wiley Periodicals, Inc.)

Objective: Critical macromolecules such as DNA maybe damaged by free radicals that are generated from the interaction of ionizing radiation with biological systems. Melatonin and vitamin C have been shown to be direct free radical scavengers. The aim of this study was to investigate the in vivo/in vitro radioprotective effects of melatonin and vitamin C separately and combined against genotoxicity induced by 6 MV x-ray irradiation in human cultured blood lymphocytes., Materials and Methods: In this experimental study, fifteen volunteers were divided into three groups of melatonin, vitamin C and melatonin plus vitamin C treatment. Peripheral blood samples were collected from each group before, and 1, 2 and 3 hours after melatonin and vitamin C administration (separately and combined). The blood samples were then irradiated with 200 cGy of 6 MV x-ray. In order to characterize chromosomal aberrations, the lymphocyte samples were cultured with mitogenic stimulus on cytokinesisblocked binucleated cells., Results: The samples collected 1hour after melatonin and vitamin C (separately and combined) ingestion exhibited a significant decrease in the incidence of micronuclei compared with their control group (P<0.05). The maximum synergic protection and reduction in frequency of micronuclei (57%) was observed 1 hour after vitamin C and melatonin administration combined., Conclusion: We conclude that simultaneous administration of melatonin and vitamin C as radioprotector substances before irradiation may reduce genotoxicity caused by x-ray irradiation.