Development of nano-liposomal human growth hormone as a topical formulation for preventing uvb-induced skin damage.

Due to its involvement in skin maintenance and repair, topical administration of recombinant human growth hormone (rhGH) is an interesting strategy for therapeutic purposes. We have formulated and characterized a topical rhGH-loaded liposomal formulation (rhGH-Lip) and evaluated its safety, biological activity, and preventive role against UVB-induced skin damage. The rhGH-Lip had an average size and zeta potential of 63 nm and -33 mV, respectively, with 70 % encapsulation efficiency. The formulation was stable at 4 °C for at least one year. The SDS-PAGE and circular dichroism results showed no structural alterations in rhGH upon encapsulation. In vitro, studies in HaCaT, HFFF-2, and Ba/F3-rhGHR cell lines confirmed the safety and biological activity of rhGH-Lip. Franz diffusion cell study showed increased rhGH skin permeation compared to free rhGH. Animal studies in nude mice showed that liposomal rhGH prevented UVB-induced epidermal hyperplasia, angiogenesis, wrinkle formation, and collagen loss, as well as improving skin moisture. The results of this study show that rhGH-Lip is a stable, safe, and effective skin delivery system and has potential as an anti-wrinkle formulation for topical application. This study also provides a new method for the topical delivery of proteins and merits further investigation.

Recent advances in molecular targeted therapy of lung cancer: Possible application in translation medicine.

Lung cancer is one of the leading causes of death among all cancer deaths. This cancer is classified into two different histological subtypes: non-small cell lung cancer (NSCLC), which is the most common subtype, and small cell lung cancer (SCLC), which is the most aggressive subtype. Understanding the molecular characteristics of lung cancer has expanded our knowledge of the cellular origins and molecular pathways affected by each of these subtypes and has contributed to the development of new therapies. Traditional treatments for lung cancer include surgery, chemotherapy, and radiotherapy. Advances in understanding the nature and specificity of lung cancer have led to the development of immunotherapy, which is the newest and most specialized treatment in the treatment of lung cancer. Each of these treatments has advantages and disadvantages and causes side effects. Today, combination therapy for lung cancer reduces side effects and increases the speed of recovery. Despite the significant progress that has been made in the treatment of lung cancer in the last decade, further research into new drugs and combination therapies is needed to extend the clinical benefits and improve outcomes in lung cancer. In this review article, we discussed common lung cancer treatments and their combinations from the most advanced to the newest.

Co-delivery of artemisinin and metformin via PEGylated niosomal nanoparticles: potential anti-cancer effect in treatment of lung cancer cells.

PURPOSE: Despite the advances in treatment, lung cancer is a global concern and necessitates the development of new treatments. Biguanides like metformin (MET) and artemisinin (ART) have recently been discovered to have anti-cancer properties. As a consequence, in the current study, the anti-cancer effect of MET and ART co-encapsulated in niosomal nanoparticles on lung cancer cells was examined to establish an innovative therapy technique. METHODS: Niosomal nanoparticles (Nio-NPs) were synthesized by thin-film hydration method, and their physicochemical properties were assessed by FTIR. The morphology of Nio-NPs was evaluated with FE-SEM and AFM. The MTT assay was applied to evaluate the cytotoxic effects of free MET, free ART, their encapsulated form with Nio-NPs, as well as their combination, on A549 cells. Apoptosis assay was utilized to detect the biological processes involved with programmed cell death. The arrest of cell cycle in response to drugs was assessed using a cell cycle assay. Following a 48-h drug treatment, the expression level of hTERT, Cyclin D1, BAX, BCL-2, Caspase 3, and 7 genes were assessed using the qRT-PCR method. RESULTS: Both MET and ART reduced the survival rate of lung cancer cells in the dose-dependent manner. The IC50 values of pure ART and MET were 195.2 µM and 14.6 mM, respectively while in nano formulated form their IC50 values decreased to 56.7 µM and 78.3 µM, respectively. The combination of MET and ART synergistically decreased the proliferation of lung cancer cells, compared to the single treatments. Importantly, the combination of MET and ART had a higher anti-proliferative impact against A549 lung cancer cells, with lower IC50 values. According to the result of Real-time PCR, hTERT, Cyclin D1, BAX, BCL-2, Caspase 3, and Caspase 7 genes expression were considerably altered in treated with combination of nano formulated MET and ART compared to single therapies. CONCLUSION: The results of this study showed that the combination of MET and ART encapsulated in Nio-NPs could be useful for the treatment of lung cancer and can increase the efficiency of lung cancer treatment.

Targeted delivery of oxaliplatin via folate-decorated niosomal nanoparticles potentiates resistance reversion of colon cancer cells.

Background: Colorectal cancer (CRC) is a prevalent type of cancer, ranking third in incidence and fourth in cancer-related deaths globally. The increase in mortality rates related to colorectal cancer among younger patients is a cause for concern. Chemotherapy is the primary approach for palliative care in colon cancer, but the development of drug resistance limits its effectiveness. Apoptosis is a process of programmed cell death that plays a crucial role in regulating normal cell death and abnormal tissue degeneration in cancer. Genes such as caspase-3, caspase-9, p53, and survivin are involved in apoptosis induction. The field of nanotechnology has presented exciting opportunities for controlled drug delivery and addressing drug resistance in cancer. Niosomes are among the nanocarriers known for their impressive features, making them excellent candidates for drug delivery. In the current study, we investigate whether niosomal nanoparticles coated with FA have the ability to deliver oxaliplatin to drug-resistant cells effectively and potentially resistance reversion in colon cancer cells. Methods: The niosomal nanoparticles (NPs) were fabricated using the thin-film hydration method and characterized using DLS (Dynamic Light Scattering), FTIR (Fourier Transform Infrared Spectroscopy), SEM (Scanning Electron Microscopy), and AFM (Atomic Force Microscopy) systems. The drug release and drug encapsulation efficiency of the NPs were also determined. An MTT assay was performed on oxaliplatin-resistant cells to determine the IC50 values of the drug in its pure and nano-encapsulated forms. Gene expression of caspase-3, caspase-9, p53, and survivin was investigated using the qRT-PCR (quantitative Reverse Transcription Polymerase Chain Reaction) technique, and cell apoptosis or necrosis was quantified using flow cytometry. Results: Size, PDI, zeta potential, morphology, drug release, and encapsulation efficiency of fabricated niosomal NPs were acceptable. Oxaliplatin anti-cancer drug showed a higher impact on cancerous cells in nano-encapsulated form. The expression level of caspase-3, caspase-9, and p53 was increased which was in confirmation by flow cytometry results. Conclusion: Taken together, results of this study demonstrated potential effect of folate decorated oxaliplatin-loaded niosomal NPs to resistance-reversion of Oxaliplatin-resistance colon cancer cells.

Fabricating niosomal-PEG nanoparticles co-loaded with metformin and silibinin for effective treatment of human lung cancer cells.

Background: Despite current therapies, lung cancer remains a global issue and requires the creation of novel treatment methods. Recent research has shown that biguanides such as metformin (MET) and silibinin (SIL) have a potential anticancer effect. As a consequence, the effectiveness of MET and SIL in combination against lung cancer cells was investigated in this study to develop an effective and novel treatment method. Methods: Niosomal nanoparticles were synthesized via the thin-film hydration method, and field emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FTIR), atomic force microscopy (AFM), and dynamic light scattering (DLS) techniques were used to evaluate their physico-chemical characteristics. The cytotoxic effects of free and drug-loaded nanoparticles (NPs), as well as their combination, on A549 cells were assessed using the MTT assay. An apoptosis test was used while under the influence of medication to identify the molecular mechanisms behind programmed cell death. With the use of a cell cycle test, it was determined whether pharmaceutical effects caused the cell cycle to stop progressing. Additionally, the qRT-PCR technique was used to evaluate the levels of hTERT, BAX, and BCL-2 gene expression after 48-h medication treatment. Results: In the cytotoxicity assay, the growth of A549 lung cancer cells was inhibited by both MET and SIL. Compared to the individual therapies, the combination of MET and SIL dramatically and synergistically decreased the IC50 values of MET and SIL in lung cancer cells. Furthermore, the combination of MET and SIL produced lower IC50 values and a better anti-proliferative effect on A549 lung cancer cells. Real-time PCR results showed that the expression levels of hTERT and BCL-2 were significantly reduced in lung cancer cell lines treated with MET and SIL compared to single treatments (p< 0.001). Conclusion: It is anticipated that the use of nano-niosomal-formed MET and SIL would improve lung cancer treatment outcomes and improve the therapeutic efficiency of lung cancer cells.

Targeted delivery of silibinin via magnetic niosomal nanoparticles: potential application in treatment of colon cancer cells.

Introduction: In recent years, various nanoparticles (NPs) have been discovered and synthesized for the targeted therapy of cancer cells. Targeted delivery increases the local concentration of therapeutics and minimizes side effects. Therefore, NPs-mediated targeted drug delivery systems have become a promising approach for the treatment of various cancers. As a result, in the current study, we aimed to design silibinin-loaded magnetic niosomes nanoparticles (MNNPs) and investigate their cytotoxicity property in colorectal cancer cell treatment. Methods: MNPs ferrofluids were prepared and encapsulated into niosomes (NIOs) by the thin film hydration method. Afterward, the morphology, size, and chemical structure of the synthesized MNNPs were evaluated using the TEM, DLS, and FT-IR techniques, respectively. Results and Discussion: The distribution number of MNNPs was obtained at about 50 nm and 70 nm with a surface charge of -19.0 mV by TEM and DLS analysis, respectively. Silibinin loading efficiency in NIOs was about 90%, and the drug release pattern showed a controlled release with a maximum amount of about 49% and 70%, within 4 h in pH = 7.4 and pH = 5.8, respectively. To investigate the cytotoxicity effect, HT-29 cells were treated with the various concentration of the drugs for 24 and 48 h and evaluated by the MTT as well as flow cytometry assays. Obtained results demonstrated promoted cell cytotoxicity of silibinin-loaded MNNPs (5-fold decrease in cell viability) compared to pure silibinin (3-fold decrease in cell viability) while had no significant cytotoxic effect on HEK-293 (normal cell line) cells, and the cellular uptake level of MNNPs by the HT-29 cell line was enhanced compared to the control group. In conclusion, silibinin-loaded MNNPs complex can be considered as an efficient treatment approach for colorectal cancer cells.

Advanced nano-therapeutic delivery of metformin: potential anti-cancer effect against human colon cancer cells through inhibition of GPR75 expression.

The high incidence rate coupled with significant mortality makes colorectal cancer one of the most prevalent and devastating cancers worldwide. Research is currently underway to explore new forms of treatment that could potentially maximize treatment outcomes while minimizing the side effects associated with conventional chemotherapy. Metformin, a natural biguanide drug, has anti-cancer properties that can inhibit the growth and proliferation of cancer cells. However, due to its short half-life and low bioavailability, the efficacy of Metf as an anti-cancer agent is limited. The purpose of this research is to assess the potency of PEGylated niosomes as a nano-delivery system for Metf, with the aim of increasing its anti-cancer effects on CaCo2 colorectal cancer cells through the effect on the expression of genes, including GPR75, hTERT, Bax, Bcl2, and Cyclin D1. Metf-loaded niosomal NPs (N-Metf) were synthesized using the thin-film hydration method and then characterized using SEM, FTIR, AFM, and DLS techniques. The release pattern of the drug from the nanoparticles (NPS) was determined using the dialysis membrane method. Furthermore, the cytotoxic effect of the metformin-loaded PEGylated niosome on the CaCo2 cell line was evaluated by the MTT test. Additionally, an apoptosis assay was conducted to assess the effect of free Metf and Metf-loaded NPS on the programmed death of the CaCo2 cells, and the impact on the cell cycle was studied through a cell cycle test. Finally, the expression levels of hTERT, Cyclin D1, BCL2, GPR75, and BAX genes were assessed in the presence of free Metf and Metf-loaded NPs by RT-PCR. Characterization experiments showed successful loading of metformin into PEGylated niosomes. The results of cytotoxicity evaluation showed that Metf-NPs had more cytotoxicity than free Metf in a dose-dependent manner. Furthermore, nuclear fragmentation and the percentage of apoptotic cells induced by Metf-NPs were significantly higher than those induced by free Metf. Additionally, Metf-NPs were found to induce more cell cycle arrest at the sub-G1 checkpoint than free Metf did. Compared with Metf-treated cells, the mRNA expression levels of GPR75, Cyclin D1, and hTERT were significantly changed in cells treated with Metf-NPs. Ultimately, it is hypothesized the nano-encapsulation of Metf into PEGylated niosomal NPs could be a worthwhile drug delivery system to enhance its effectiveness in treating colorectal cancer cells.

Potential application of inorganic nano-materials in modulation of macrophage function: Possible application in bone tissue engineering.

Nanomaterials indicate unique physicochemical properties for drug delivery in osteogenesis. Benefiting from high surface area grades, high volume ratio, ease of functionalization by biological targeting moieties, and small size empower nanomaterials to pass through biological barriers for efficient targeting. Inorganic nanomaterials for bone regeneration include inorganic synthetic polymers, ceramic nanoparticles, metallic nanoparticles, and magnetic nanoparticles. These nanoparticles can effectively modulate macrophage polarization and function, as one of the leading players in osteogenesis. Bone healing procedures in close cooperation with the immune system. Inflammation is one of the leading triggers of the bone fracture healing barrier. Macrophages commence anti-inflammatory signaling along with revascularization in the damaged site to promote the formation of a soft callus, bone mineralization, and bone remodeling. In this review, we will discuss the role of macrophages in bone hemostasis and regeneration. Furthermore, we will summarize the influence of the various inorganic nanoparticles on macrophage polarization and function in the benefit of osteogenesis.

Fabrication of Antibody Conjugated Super Magnetic Oxide Nanoparticles for Early Detection of Prostate Cancer.

BACKGROUND: Prostate cancer is one of the most widespread cancers in the world. Early diagnosis is the most important factor in treatment efficiency. Furthermore, new methods for early diagnosis and treatment play an important role. In this study, we designed targeted conjugation of antibodies with iron nanoparticles and evaluated the binding properties of antibodies to prostate cancers and benign tissues. This method in addition to having a lower cost has high sensitivity and specificity. METHODS: Anti- PSCA antibodies were purified and conjugated to super magnetic oxide nanoparticles (SPION). Then, iron staining on prostate adenocarcinoma tissues was performed. At the same time, immunohistochemically staining was performed on similar tissues to compare the results. In addition, benign prostatic hyperplasia (BPH) samples were used as a control sample. RESULTS: In adenocarcinoma tissues with iron staining, many blue spots are seen compared to benign tissues, and the number of these spots increases with increasing tumor grade. CONCLUSION: These findings indicate the characteristic of iron staining as a conjugate antibody to iron can be an appropriate approach to specific staining of tumor markers in cancer tissues and can be used to diagnose prostate cancer due to its safety, low cost, sensitivity, and specificity.

In Vitro Efficacy of Curcumin-Loaded Amine-Functionalized Mesoporous Silica Nanoparticles against MCF-7 Breast Cancer Cells.

Purpose: Mesoporous silica nanoparticles (MSNs) have drawn substantial interest as drug nanocarriers for breast cancer therapy. Nevertheless, because of the hydrophilic surfaces, the loading of well-known hydrophobic polyphenol anticancer agent curcumin (Curc) into MSNs is usually very low. Methods: For this purpose, Curc molecules were loaded into amine-functionalized MSNs (MSNs-NH2 -Curc) and characterized using thermal gravimetric analysis (TGA), Fourier-transform infrared (FTIR), field emission scanning electron microscope (FE-SEM), transmission electron microscope (TEM), Brunauer-Emmett-Teller (BET). MTT assay and confocal microscopy, respectively, were used to determine the cytotoxicity and cellular uptake of the MSNs-NH2 - Curc in the MCF-7 breast cancer cells. Besides, the expression levels of apoptotic genes were evaluated via quantitative polymerase chain reaction (qPCR) and western blot. Results: It was revealed that MSNs-NH2 possessed high values of drug loading efficiency and exhibited slow and sustained drug release compared to bare MSNs. According to the MTT findings, while the MSNs-NH2 -Curc were nontoxic to the human non-tumorigenic MCF-10A cells at low concentrations, it could considerably decrease the viability of MCF-7 breast cancer cells compared to the free Curc in all concentrations after 24, 48 and 72 hours exposure times. A cellular uptake study using confocal fluorescence microscopy confirmed the higher cytotoxicity of MSNs-NH2 -Curc in MCF-7 cells. Further, it was found that the MSNs-NH2 -Curc could drastically affect the mRNA and protein levels of Bax, Bcl-2, caspase 3, caspase 9, and hTERT relative to the free Curc treatment. Conclusion: Taken together, these preliminary results suggest the amine-functionalized MSNs-based drug delivery platform as a promising alternative approach for Curc loading and safe breast cancer treatment.

G Protein-Coupled Receptor 75 (GPR75) As a Novel Molecule for Targeted Therapy of Cancer and Metabolic Syndrome.

In recent years, molecular targeted therapy has attracted more attention from researchers due to its high efficiency and fewer side effects. Researchers are attempting to find more specific ways to treat diseases. It has been found that there are different targets for the treatment of diseases such as cancer, obesity, and metabolic syndrome. It is important to find a potential target in order to lessen the side effects of current treatments. G Protein-coupled receptors (GPCRs) are a large family of transmembrane proteins that are expressed in many organs, leading to the activation of internal signal transduction cascades through the binding of different ligands, including neurotransmitters, peptides, and lipids. Due to the critical role of GPCRs in cells, it could be a potential target. G protein-coupled receptor 75 (GPR75) is a novel member of the GPCR family that has an important role in many diseases, such as obesity, cancer, and metabolic syndrome. Until now, three ligands have been detected for GPR75, including 20-HETE, CCL5, and RANTES. Recent studies suggest that 20-HETE, through GPR75, triggers signaling pathways including PI3K/Akt and RAS/MAPK, leading to a more aggressive phenotype in prostate cancer cells. Additionally, the PI3K/Akt and RAS/MAPK signaling pathways activate NF-κB, which is significant in various pathways of cancer development such as proliferation, migration, and apoptosis. The findings indicate that inhibiting GPR75 in humans leads to an increase in insulin sensitivity and glucose tolerance, as well as a reduction in body fat storage. According to these discoveries, GPR75 could be a potential target for drug treatment of diseases such as obesity, metabolic syndrome, and cancer. In this review, we aimed to discuss the therapeutic impact of GPR75 in cancer, metabolic syndrome, and obesity and underscore the possible pathways.

Allelic burden of Janus kinase 2 in a 6-month course of therapy for myeloproliferative neoplasms.

BACKGROUND: Janus kinase 2 (JAK2) V617F gene mutation is an important marker for the diagnosis of Philadelphia negative Myeloproliferative neoplasms (MPN) which is subdivided into Polycythemia Vera (PV), Primary Myelofibrosis (PMF), and Essential Thrombocythemia (ET). The aim here is to investigate the JAK2 allele burden of the patients diagnosed with the subgroups of MPN and to demonstrate the alterations of hematological parameters and spleen size between diagnosis and 6 months of treatment. METHODS: A total of 107 patients with the diagnosis of MPN and negative Philadelphia chromosome, 51 males and 56 females with a mean age of 59,74 ± 16,41 years, were included in the study. Diagnosis of MPN was based on the World Health Organization (WHO) criteria. Subgroups of MPN distributed as 49,5% ET, 46,7% PV, and 3,8% PMF. Findings such as the age of the patients, JAK-2 allele burden, and laboratory findings of splenomegaly were examined at the time of diagnosis, 3rd month, and 6th month. JAK2 allele burden and spleen size were re-evaluated in 6th month. RESULTS: Our study confirmed the findings of high Hb, HCT, and RBC but low platelet values in PV patients with high JAK2 allele burden with respect to other groups, a positive correlation between JAK2 allele burden and LDH. CONCLUSIONS: A novel finding of our study is, that there is not any reducing effect of the phlebotomy on JAK2 allele burden in PV patients whether they receive phlebotomy or not. Evaluation of the spleen size alteration during 6 months within the subgroups demonstrated a decrease in PV and ET groups whereas no statistically significant difference was found in the PMF group.

An update on the effect of intra-articular intervention strategies using nanomaterials in osteoarthritis: Possible clinical application.

Osteoarthritis (OA) is the most common progressive condition affecting joints. It mainly affects the knees and hips as predominant weight-bearing joints. Knee osteoarthritis (KOA) accounts for a large proportion of osteoarthritis and presents numerous symptoms that impair quality of life, such as stiffness, pain, dysfunction, and even deformity. For more than two decades, intra-articular (IA) treatment options for managing knee osteoarthritis have included analgesics, hyaluronic acid (HA), corticosteroids, and some unproven alternative therapies. Before effective disease-modifying treatments for knee osteoarthritis, treatments are primarily symptomatic, mainly including intra-articular corticosteroids and hyaluronic acid, so these agents represent the most frequently used class of drugs for managing knee osteoarthritis. But research suggests other factors, such as the placebo effect, have an essential role in the effectiveness of these drugs. Several novel intra-articular therapies are currently in the clinical trial processes, such as biological therapies, gene and cell therapies. Besides, it has been shown that the development of novel drug nanocarriers and delivery systems could improve the effectiveness of therapeutic agents in osteoarthritis. This review discusses the various treatment methods and delivery systems for knee osteoarthritis and the new agents that have been introduced or are in development.

Design and optimization various formulations of PEGylated niosomal nanoparticles loaded with phytochemical agents: potential anti-cancer effects against human lung cancer cells.

BACKGROUND: Phytochemicals and their derivatives are good options to improve treatment efficiency in cancer patients. Artemisinin (ART) and metformin (MET) are widely used phytochemicals to treat various types of cancers. However, their application because of their dose-dependent side effects, and poor bioavailability brings several challenges. Niosome is a novel nanocarrier that is the best choice to encapsulate both lipophilic and hydrophilic drugs. In this study, we synthesized and characterized various formulations of PEGylated (polyethylene glycol) niosomal nanoparticles co-loaded with ART-MET and evaluated their anticancer effect on A549 lung cancer cells. METHODS: Various formulations of PEGylated noisome were prepared by the thin-film hydration method and characterized in size, morphology, release pattern, and physicochemical structure. The cytotoxic effect of the free ART-MET and optimized PEGylated niosomal nanoparticles loaded with ART-MET on A549 cells were evaluated by MTT assay. Furthermore, the Real-time PCR (RT-PCR) technique used to evaluate apoptotic and anti-apoptotic gene expression. RESULTS: The size, encapsulation efficiency (EE), and polydispersity index (PDI) of the optimized nanoparticles are 256 nm, 95%, and 0.202, respectively. Additionally, due to the PEGylation hydrophilic character, there is a major consideration of the high impact of PEGylation on reducing niosome size. According to the results of the MTT assay, free ART-MET and ART-MET-loaded niosomal nanoparticles showed dose-dependent toxicity and inhibits the growth of A549 lung cancer cells. Furthermore, the RT-PCR results indicated that ART-MET-loaded niosomal nanoparticles have a higher anti-proliferative effect by inhibiting anti-apoptotic and inducing apoptotic gene expression in A549 lung cancer cells. CONCLUSIONS: Our study revealed that the simultaneous use of ART and MET in the optimized PEGylated niosomal nanoparticles delivery system could be an appropriate approach to improve the effectiveness of lung cancer treatment.

The Role of Interferons in Long Covid Infection.

Although the new generation of vaccines and anti-COVID-19 treatment regimens facilitated the management of acute COVID-19 infections, concerns about post-COVID-19 syndrome or Long Covid are rising. This issue can increase the incidence and morbidity of diseases such as diabetes, and cardiovascular, and lung infections, especially among patients suffering from neurodegenerative disease, cardiac arrhythmias, and ischemia. There are numerous risk factors that cause COVID-19 patients to experience post-COVID-19 syndrome. Three potential causes attributed to this disorder include immune dysregulation, viral persistence, and autoimmunity. Interferons (IFNs) are crucial in all aspects of post-COVID-19 syndrome etiology. In this review, we discuss the critical and double-edged role of IFNs in post-COVID-19 syndrome and how innovative biomedical approaches that target IFNs can reduce the occurrence of Long Covid infection.

Potentiation of Folate-Functionalized PLGA-PEG nanoparticles loaded with metformin for the treatment of breast Cancer: possible clinical application.

AIM: Folate receptor expression increase up to 30% in breast cancer cells and could be used as a possible ligand to couple to folate-functionalized nanoparticles. Metformin (Met) is an anti-hyperglycemic agent whose anti-cancer properties have been formerly reported. Consequently, in the current study, we aimed to synthesize and characterize folate-functionalized PLGA-PEG NPs loaded with Met and evaluate the anti-cancer effect against the MDA-MB-231 human breast cancer cell line. METHODS: FA-PLGA-PEG NPs were synthesized by employing the W1/O/W2 technique and their physicochemical features were evaluated by FE-SEM, TEM, FTIR, and DLS methods. The cytotoxic effects of free and Nano-encapsulated drugs were analyzed by the MTT technique. Furthermore, RT-PCR technique was employed to assess the expression levels of apoptotic and anti-apoptotic genes. RESULT: MTT result indicated Met-loaded FA-PLGA-PEG NPs exhibited cytotoxic effects in a dose-dependently manner and had more cytotoxic effects relative to other groups. The remarkable down-regulation (hTERT and Bcl-2) and up-regulation (Caspase7, Caspase3, Bax, and p53) gene expression were shown in treated MDA-MB-231 cells with Met-loaded FA-PLGA-PEG NPs. CONCLUSION: Folate-Functionalized PLGA-PEG Nanoparticles are suggested as an appropriate approach to elevate the anticancer properties of Met for improving the treatment effectiveness of breast cancer cells.

Potential Anti-Cancer Effect of Helenalin as a Natural Bioactive Compound on the Growth and Telomerase Gene Expression in Breast Cancer Cell Line.

OBJECTIVE: The telomerase gene is overexpressed in the majority of tumors and cancers compared to normal and healthy cells, and on the other hand, this enzymatic protein is overactive, therefore, the telomerase enzyme is considered a primary target for diagnostic and therapeutic purposes in most cancers. This has been hypothesized that Helenalin has anti-telomerase activity in a wide range of cancers and Tumor tissues. In this study, we investigated the inhibitory effect of helenalin extract on telomerase gene expression in the T47D breast cancer cell line. METHODS: We used the MTT assay to evaluate the cytotoxic effect of different concentrations of helenalin on the T47D breast cancer cell line at 24, 48, and 72 hours. Besides, the expression of the hTERT gene in T47D cell lines treated with 1.0 and 5.0 µM helenalin after 24, 48, and 72 h incubation times was investigated through real-time PCR. RESULTS: According to the MTT assay, the inhibitory effect of helenalin on T47D cell proliferation is time and dose-dependent. Moreover, the results of Real-time PCR showed that exposure of T47D cell lines to helenalin led to a significant Decreasing in the expressional values of the hTERT gene as a time and dose-dependent procedure compared with the control group (P ≤ 0.05). CONCLUSION: These preliminary results demonstrated the cytotoxic potential of helenalin through inhibition of hTERT against T47D breast cancer cells.

Design and development of biodegradable POSS-PCL-Zeolite (ß) nano-scaffold for potential applications in bone regeneration.

Side effects caused by bone fractures and restrictions on bone regeneration impose an enormous economic burden on the health system of society. To overcome these limitations, tissue engineering and cell-based therapies have been proposed as alternatives to induce and promote bone healing. Still, bone regeneration disadvantages, such as limited and painful surgery, the risk of infection, nerve injury, bleeding, and function damage, have led investigators to find an alternative therapy. In some studies, bone stimulants have prompted scientists to design scaffolds with appropriate physical structure with the possibility of cell adhesion and proliferation, which plays an influential role in the regeneration and repair of bone tissue. PCL nanofiber is an absorbing candidate for the formulation of biocompatible scaffolds used in tissue engineering. To overcome these negative aspects, improve the properties of PCL nanofibers, and based on the biocompatibility and superior mechanical properties of POSS, Polyhedral Oligomeric Silsesquioxane-Polycaprolactone-Zeolite (POSS-PCL-Zeolite) nanocomposite electrospun nanofiber scaffolds were fabricated in the present study. Nanohybrids and nanofibers structures were characterized by FTIR, HNMR, XRD, SEM, EDX, and DSC techniques. We used cellular and molecular assays, including DCFH ROS detection system, gene expression (RUNX-2, Osteocalcin, Nrf2, BAX, VEGF gens), and apoptotic to demonstrate the biocompatibility and induce bone differentiation of formulated POSS-PCL-Zeolite scaffolds. The results showed the biodegradability of POSS-PCL-Zeolite Nano-scaffold and supported the nesting of mesenchymal stem cells (MSCs) and induced bone differentiation by POSS-PCL-Zeolite Nano-scaffold.

Synthesis and characterization of N-rich fluorescent bio-dots as a reporter in the design of dual-labeled FRET probe for TaqMan PCR: A feasibility study.

DNA-based analytical techniques have provided an advantageous sensing assay in the realm of biotechnology. Bio-inspired fluorescent nanodots are a novel type of biological staining agents with excellent optical properties widely used for cellular imaging and diagnostics. In the present research, we successfully synthesized bio-dots with excellent optical properties and high-quantum yield from DNA sodium salt through the hydrothermal method. We conjugated the bio-dots with 3' Eclipse Dark Quencher (Eclipse)-labeled single-strand oligodeoxyribonucleotide according to carbodiimide chemistry, to design a fluorescence resonance energy transfer (FRET) probe. The results confirmed the prosperous synthesis and surface functionalization of the bio-dot. Analysis of size, zeta potential, and FTIR spectroscopy verified successful bioconjugation of the bio-dots with probes. UV-visibility analysis and fluorescence intensity profile of the bio-dot and bio-dot@probes represented a concentration-dependent quenching of fluorescent signal of bio-dot by Eclipse after probe conjugation. The results demonstrated that TaqMan PCR was not feasible using the designed bio-dot@probes. Our results indicated that bio-dot can be used as an efficient fluorescent tag in the design of fluorescently labeled oligonucleotides with high biocompatibility and optical features.

A dual synergistic effect of titanium and curcumin co-embedded on extracellular matrix hydrogels of decellularized bone: Potential application in osteoblastic differentiation of adipose-derived mesenchymal stem cells.

This research aims to design and fabricate a novel hydrogel-based composite as a functional biomimetic and biocompatible scaffold for amended osteoblastic differentiation of adipose-derived mesenchymal stem cells (ADMSCs). The extracellular matrix (ECM) hydrogel is an ideal scaffold in tissue engineering in terms of its structure mimics natural tissue. In this study, the fresh bovine femur was demineralized and decellularized; next, ECM hydrogel was obtained by digesting these matrices. Then, TiO2 and curcumin-loaded hydrogel (Hy/Ti/Cur) was fabricated besides TiO2-loaded hydrogel (Hy/Ti) and curcumin-loaded hydrogel (Hy/Cur). Comparing the scanning electron microscopy (SEM) images of the pure network hydrogel and the rough morphology of Hy/Ti/Cur revealed that curcumin and titanium dioxide were successfully loaded into the hydrogel. In addition, FTIR spectroscopy and X-ray diffraction (XRD) validated these findings. The findings of the hydrogels' swelling test indicated the favourable impact of curcumin and titanium dioxide in hydrogels, which enhances water absorption capacity. Our results showed that the hydrogels were cytocompatible, and the cell viability on the hydrogels was elevated compared to the control. The synergistic effect of TiO2 and Cur co-embedded on ECM hydrogel (Hy/Ti/Cur) stimulates bone differentiation markers, such as Runt-related transcription factor 2 (RUNX-2) and osteocalcin (OCN) in ADMSCs cultured in normal and osteogenic medium. Moreover, Alkaline Phosphatase (ALP) activity and calcium deposition of ADMSCs cultured on engineered hydrogels were increased. These experiments showed that newly fabricated hydrogel has the potential to induce osteogenesis, which is recommended as an attractive scaffold in bone tissue engineering.