Rational peptide design for targeting cancer cell invasion.

Cell invasion is an important process in cancer progression and recurrence. Invasion and implantation of cancer cells from their original place to other tissues, by disabling vital organs, challenges the treatment of cancer patients. Given the importance of the matter, many molecular treatments have been developed to inhibit cancer cell invasion. Because of their low production cost and ease of production, peptides are valuable therapeutic molecules for inhibiting cancer cell invasion. In recent years, advances in the field of computational biology have facilitated the design of anti-cancer peptides. In our investigation, using computational biology approaches such as evolutionary analysis, residue scanning, protein-peptide interaction analysis, molecular dynamics, and free energy analysis, our team designed a peptide library with about 100 000 candidates based on A6 (acetyl-KPSSPPEE-amino) sequence which is an anti-invasion peptide. During computational studies, two of the designed peptides that give the highest scores and showed the greatest sequence similarity to A6 were entered into the experimental analysis workflow for further analysis. In experimental analysis steps, the anti-metastatic potency and other therapeutic effects of designed peptides were evaluated using MTT assay, RT-qPCR, zymography analysis, and invasion assay. Our study disclosed that the IK1 (acetyl-RPSFPPEE-amino) peptide, like A6, has great potency to inhibit the invasion of cancer cells.

Combined Treatment of Dendrosomal-Curcumin and Daunorubicin Synergistically Inhibit Cell Proliferation, Migration and Induce Apoptosis in A549 Lung Cancer Cells.

Purpose: Chemotherapy drugs used to treat lung cancer are associated with drug resistance and severe side effects. There have been rising demands for new therapeutic candidates and novel approaches, including combination therapy. Here, we aimed to investigate the combinatorial effect of a dendrosomal formulation of curcumin (DNC) and daunorubicin (DNR) on the A549 lung cancer cell line. Methods: We performed cytotoxicity, apoptosis, cell migration, colony-formation capacity, and gene expression analysis to interpret the mechanism of action for a combination of DNC and DNR on A549 cells. Results: Our results revealed that the combination of DNC and DNR could synergistically inhibit the A549 cells' growth. This synergistic cytotoxicity was further approved by flow cytometry, migration assessment, colony-forming capacity and gene expression analysis. DNR combination with DNC resulted in increased apoptosis to necrosis ratio compared to DNR alone. In addition, the migration and colony-forming capacity were at the minimal range when DNC was combined with DNR. Combined treatment decreased the expression level of MDR-1, hTERT and Bcl-2 genes significantly. In addition, the ratio of Bax/Bcl2 gene expression significantly increased. Our analysis by free curcumin, dendrosomes and DNC also showed that dendrosomes do not have any significant cytotoxic effect on the A549 cells, suggesting that this carrier has a high potential for enhancing the curcumin's biological effects. Conclusion: Our observations suggest that the DNC formulation of curcumin synergistically enhances the antineoplastic effect of DNR on the A549 cell line through the modulation of apoptosis/necrosis ratio, as well as Bax/Bcl2 ratio, MDR-1 and hTERT gene expression.

Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells.

BACKGROUND: Paliurus spina-christi Mill. (PSC) fruit is frequently used in the treatment of diabetes mellitus in Mediterranean regions. Here, we investigated the effects of various PSC fruit extracts (PSC-FEs) on glucose consumption and some key mediators of insulin signaling pathways in high glucose and high insulin-induced insulin-resistant HepG2 cells. METHODS: The effects of methanolic, chloroform and total extracts on cell proliferation were assessed by the MTT assay. The potential of non-toxic extracts on glucose utilization in insulin-resistant HepG2 cells was checked using a glucose oxidase assay. AKT and AMP-activated protein kinase (AMPK) pathway activation and mRNA expression levels of insulin receptor (INSR), glucose transporter 1 (GLUT1), and glucose transporters 4 (GLUT4) were determined by western blotting and real-time PCR, respectively. RESULTS: We found that high concentrations of methanolic and both low and high concentrations of total extracts were able to enhance glucose uptake in an insulin-resistant cell line model. Moreover, AKT and AMPK phosphorylation were significantly increased by the high strength of methanolic extract, while total extract raised AMPK activation at low and high concentrations. Also, GLUT 1, GLUT 4, and INSR were elevated by both methanolic and total extracts. CONCLUSIONS: Ultimately, our results shed new light on methanolic and total PSC-FEs as sources of potential anti-diabetic medications, restoring glucose consumption and uptake in insulin-resistant HepG2 cells. These could be at least in part due to re-activating AKT and AMPK signaling pathways and also increased expression of INSR, GLUT1, and GLUT4. Overall, active constituents present in methanolic and total extracts of PCS are appropriate anti-diabetic agents and explain the use of these PSC fruits in traditional medicine for the treatment of diabetes.

Fabrication of a microfluidic device for probiotic drug's dosage screening: Precision Medicine for Breast Cancer Treatment.

Breast cancer is the most common cancer in women; it has been affecting the lives of millions each year globally and microfluidic devices seem to be a promising method for the future advancements in this field. This research uses a dynamic cell culture condition in a microfluidic concentration gradient device, helping us to assess breast anticancer activities of probiotic strains against MCF-7 cells. It has been shown that MCF-7 cells could grow and proliferate for at least 24 h; however, a specific concentration of probiotic supernatant could induce more cell death signaling population after 48 h. One of our key findings was that our evaluated optimum dose (7.8 mg/L) was less than the conventional static cell culture treatment dose (12 mg/L). To determine the most effective dose over time and the percentage of apoptosis versus necrosis, flowcytometric assessment was performed. Exposing the MCF-7 cells to probiotic supernatant after 6, 24 and 48 h, confirmed that the apoptotic and necrotic cell death signaling were concentration and time dependent. We have shown a case that these types of microfluidics platforms performing dynamic cell culture could be beneficial in personalized medicine and cancer therapy.

Structural evolution of Delta lineage of SARS-CoV-2.

One of the main obstacles in prevention and treatment of COVID-19 is the rapid evolution of the SARS-CoV-2 Spike protein. Given that Spike is the main target of common treatments of COVID-19, mutations occurring at this virulent factor can affect the effectiveness of treatments. The B.1.617.2 lineage of SARS-CoV-2, being characterized by many Spike mutations inside and outside of its receptor-binding domain (RBD), shows high infectivity and relative resistance to existing cures. Here, utilizing a wide range of computational biology approaches, such as immunoinformatics, molecular dynamics (MD), analysis of intrinsically disordered regions (IDRs), protein-protein interaction analyses, residue scanning, and free energy calculations, we examine the structural and biological attributes of the B.1.617.2 Spike protein. Furthermore, the antibody design protocol of Rosetta was implemented for evaluation the stability and affinity improvement of the Bamlanivimab (LY-CoV55) antibody, which is not capable of interactions with the B.1.617.2 Spike. We observed that the detected mutations in the Spike of the B1.617.2 variant of concern can cause extensive structural changes compatible with the described variation in immunogenicity, secondary and tertiary structure, oligomerization potency, Furin cleavability, and drug targetability. Compared to the Spike of Wuhan lineage, the B.1.617.2 Spike is more stable and binds to the Angiotensin-converting enzyme 2 (ACE2) with higher affinity.

Protective effect of selenium on vincristine-induced peripheral neuropathy in PC12 cell line.

Vincristine-induced peripheral neuropathy (VIPN) is the main side effect and major reason for neuropathic pain in cancer survivors treated with vincristine. Vincristine, a chemotherapeutic antimitotic drug, is used frequently in combination chemotherapy. The primary purpose of the current study was to assess the protective effect of sodium selenite (SSe) on VIPN in vitro. Cytotoxicity effects of vincristine were evaluated using PC12 cells as a neuronal model. The cell culture studies were conducted in three groups based on the various treatments, including vincristine, SSe, and co-exposure to both compositions. Cell viability and cell cycle analyses were performed using MTT assay and flow cytometry, respectively. The level of mRNA expression of Bax and Bcl-2 was determined using qRT-PCR. According to the results, vincristine decreased the survival rate of PC12 cells. After 24 and 48 h exposure to different concentrations of vincristine (0.1-20 µΜ), the survival rate of PC12 cells decreased as compared to the control group. The results showed that treatment with 5 µΜ of vincristine resulted in apoptosis of PC12 cells. Interestingly,co-incubation of these cells with SSe significantly reduced the cell damage induced by vincristine. Furthermore, vincristine induced the inhibition of the G2 phase in PC 12 cells, and using SSe in combination with vincristine eliminated the inhibition of the cell cycle in the G2 phase. Briefly, our in vitro preliminary study showed that SSe might protect PC12 cells from vincristine-induced peripheral neuropathy during chemotherapy.

Metformin exerts synergistic anti-proliferative effects with liraglutide in human umbilical vein endothelial cells (HUVECs).

Objectives: Metformin (Met) and liraglutide (Lira) have been approved to treat type 2 diabetes mellitus and have cardioprotective effects. Materials and Methods: Human umbilical vein endothelial cells (HUVECs) were incubated with Met, Lira, or their combination in this study. Results: Results showed that the synergistic inhibitory effect of the two drugs on HUVECs proliferation was significant (75%) after 48 hr drug exposure. In addition, either Lira or Met alone had a marked tendency to inhibit the migration of HUVECs (42% and 39%). Almost a complete inhibition (97%) was demonstrated in combinational use after 48 hr treatment. After combining these two drugs, the apoptosis rate raised to 68%, which was a significant approval of synergistic apoptosis induction of Met and Lira. The combinational group indicated a substantial increase in VEGF, PDGF, and MMP-9 at 24 hr compared with the control. Conclusion: This study showed that combination therapy with Lira and Met could effectively reduce cell proliferation, induce apoptosis, and inhibit cell migration in the HUVECs. This study provides evidence to support using Met in combination with Lira as a treatment option for patients with type-2 diabetes and cancer.

Production and Conjugation of Truncated Recombinant Diphtheria Toxin to VEGFR-2 Specific Nanobody and Evaluation of its Cytotoxic Effect on PC-3 Cell Line.

Immunotoxins have represented a great potency in targeted therapeutics to encounter tumors. They consist of a protein toxin conjugated to a targeting moiety, which recognizes a specific antigen on surface of cancer cells and accordingly induces cell death by toxin segment. The targeting part could be a nanobody, which is a group of antibodies composed of an only functional single variable heavy chain (VHH).Therefore, this study was done to produce an immunotoxin (VGRNb-DT) by chemical conjugation of a truncated diphtheria toxin moiety to an anti-vascular endothelial growth factor receptor 2(VEGFR-2) nanobody, and to identify effectiveness of immunotoxin in recognizing the VEGFR-2- positive cancer cells and inhibiting cell growth and survival. Diphtheria toxin was expressed and purified by nickel affinity chromatography, and accordingly, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis confirmed its expression. Function of heterobifunctional crosslinkers, Sulfo-SMCC (sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate), and SATP (N-succinimidyl-S- acetylthiopropionate) for bioconjugation purposes was acknowledged by cation exchange high-performance liquid chromatography (HPLC). Cytotoxicity of immunotoxin was evaluated on the VEGFR-2 positive PC-3 cell line by MTT assay. Overexpression of VEGFR-2 in the PC-3 cell line allowed immunotoxin to recognize them by anti-VEGFR-2 nanobodies. The concentrations above 5 µg/ml represented a significant decrease in cell survival rate in PC-3 cells compared to HEK293 cells (VEGFR-2 negative cells) as controls.VGRNb-DT demonstrated a successful bioconjugation; furthermore, variable concentrations were correlated with cell death in prostate cancer PC-3 cells.

Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND: Sitagliptin is known as an antidiabetic agent inhibiting the dipeptidyl peptidase-4. Although sitagliptin may influence weight, controversial results have been reported, and there is no general agreement on this issue. Therefore, this study assessed the effect of sitagliptin as monotherapy and add-on therapy to metformin on weight reduction in overweight or obese cases with type 2 diabetes. METHODS: We reviewed the following databases to identify all relevant papers published until 1st April 2021: Web of Science, MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials Cochrane Library, and Google Scholar. The research included all clinical trials investigating the effect of sitagliptin in obese or overweight adult patients with type 2 diabetes without any language restriction. RESULTS: In total, eighteen randomized controlled trials with 2009 participants were included in our meta-analysis. Results showed supplementation of sitagliptin has led to weight loss for sitagliptin treated (MD -0.99; 95% CI; (-1.87, -0.12); p=0.026)) and sitagliptin+metformin treated groups (MD -1.09; 95% CI; (-1.69, -0.49); p<0.001)). Also, the intervention has influenced body mass index in sitagliptin treated (MD -0.23; 95% CI; (-0.45, 0.02); p=0.033)) and sitagliptin+metformin treated groups (MD -0.52; 95% CI; (-0.96, 0.08); p=0.020)) comparing to placebo. CONCLUSION: Our results demonstrated that sitagliptin administration with or without metformin might reduce the body weight and body mass index if these drugs are taken for more than 6 months.

A Review of Therapeutic Antibodies in Breast Cancer.

Since the first production of monoclonal antibodies about 35 years ago, researchers have found them useful in the treatment and diagnosis of various diseases such as cancer. By developing different types of monoclonal antibodies such as humanized, drug conjugated, or bispecific ones, researchers, have achieved remarkable success in treating several complicated and challenging diseases, targeting specific antigens or receptors makes monoclonal antibodies the right choice to inhibit signaling pathways like programmed death-ligand 1 (PD-L1) or programmed death1 (PD-1) and changing cell behavior. As one of the most common types of malignancies among women, breast cancer is one of the most critical conditions which different types of monoclonal antibodies were designed and produced to treat. Therefore, we reviewed these antibodies in breast cancer, their targets, and their efficacy and toxicity, with more focus on recent PD-L1or PD-1 inhibitor antibodies in breast cancer and beyond.

CD44 polymorphisms and its variants, as an inconsistent marker in cancer investigations.

Among cell surface markers, CD44 is considered the main marker for identifying and isolating the cancer stem cells (CSCs) among other cells and has attracted significant attention in a variety of research areas. Many studies have shown the essential roles of CD44 in initiation, metastasis, and tumorigenesis in different types of cancer; however, the validity of CD44 as a therapeutic or diagnostic target has not been fully confirmed in some other studies. Whereas the association of specific single nucleotide polymorphisms (SNPs) in the CD44 gene and related variants with cancer risk have been observed in clinical investigations, the significance of these findings remains controversial. Here, we aimed to provide an up-to-date overview of recent studies on the association of CD44 polymorphisms and its variants with different kinds of cancer to determine whether or not it can be used as an appropriate candidate for cancer tracking.

A review of potential suggested drugs for coronavirus disease (COVID-19) treatment.

The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79% and 50% genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they are not specific and targeted. Therefore, several drugs have been investigated for their efficacy and safety in the treatment of COVID-19; most of them are undergoing clinical trials. This article summarizes clinical investigations of potential therapeutic drugs used as COVID-19 therapy. Subsequently, it prepares a pattern of results and therapeutic targets to help further experiment designs. We have investigated drugs as classified in the following three groups; 1) The drugs which computationally showed effectiveness (in silico) but needed further lab confirmations; 2) Emetine, Teicoplanin, and Nelfinavir have shown effectiveness in vitro; 3) The drugs currently under clinical trial.

Growth Promotion and Increased ATP-Binding Cassette Transporters Expression by Liraglutide in Triple Negative Breast Cancer Cell Line MDA-MB-231.

BACKGROUND: Glucagon-like petide-1 (GLP-1) agonists such as liraglutide are widely employed in type 2 diabetes due to their glucose reducing properties and small risk of hypoglycemia. Recently, it has been shown that GLP-1agonists can inhibit breast cancer cells growth. Nonetheless, concerns are remained about liraglutide tumor promoting effects as stated by population studies. MATERIAL AND METHODS: We evaluated the effects liraglutide on proliferation of MDA-MB-231 cells by MTT assay and then ATP-binding cassette (ABC) transporters expressions assessed by Real time PCR. Statistical comparisons were made using one-way analysis of variance followed by a post hoc Dunnett test. RESULTS: Here, we report that liraglutide can stimulate the growth of highly invasive triple negative cell line MDA-MB-231; which can be attributed to AMPK-dependent epithelial-mesenchymal transition (EMT) happening in MDA-MB-231 context. Toxicity effects were only observed with concentrations far above the serum liraglutide concentration. ATP-binding cassette (ABC) transporters expressions were upregulated, indicating the possible drug resistance and increased EMT. CONCLUSION: In conclusion, these results suggest that liraglutide should be used with caution in patients who are suffering or have the personal history of triple negative breast cancer. However, more detailed studies are required to deepen understanding of liraglutide consequences in triple negative breast cancer. ▶Graphical Abstract.

Synergistic Cytotoxic and Apoptotic Effects of Local Probiotic Lactobacillus Brevis Isolated from Regional Dairy Products in Combination with Tamoxifen.

Tamoxifen (TAM), the most widely used anti-estrogenic drug, inhibits the progression of breast cancer through competing with estrogen for binding to the estrogen receptor (ER). Tamoxifen has been the first-line adjuvant endocrine therapy in pre- and postmenopausal patients with ER + breast cancer for two decades. However, due to its side effects, interest in using anticancer agents derived from natural foods has increased. It has recently been stated that some probiotics can improve the efficacy of anticancer drugs via synergistic effects. Here, Local Probiotic Lactobacillus Brevis were isolated and characterized from dairy products and its supernatant was prepared. Proliferation of MCF-7, a breast cancer cell line, was investigated after treatment with Lactobacillus Brevis supernatant (LBS) solely, and in combination with Tamoxifen. In Vitro trials were performed to assess the LBS potency. Bax and Bcl-2 mRNA expression levels and apoptotic effects after these treatments were examined by qRT-PCR and flow cytometry, respectively. The results indicated that LBS induces apoptosis in MCF-7 at high concentrations. Transcription of Bcl-2 was reduced but Bax mRNA expression was enhanced. Tamoxifen's inhibitory effect on the cell growth was synergistically augmented by LBS. In addition, we found that the Bcl-2 mRNA levels in the cells exposed to TAM/LBS were lower than in those treated with TAM alone. Our findings suggest potential role of LB as an adjuvant therapy in cancer treatment and prevention; along with its underlying mechanism.

Combination of Curcumin and Metformin Inhibits Cell Growth and Induces Apoptosis without Affecting the Cell Cycle in LNCaP Prostate Cancer Cell Line.

Side effects and chemotherapy resistance, demand new therapeutics with minimal side effects. Here, we investigated the combined effect of curcumin and metformin on the LNCaP prostate cancer cell line. LNCaP cells were treated with curcumin, metformin, and their combination at different concentrations. Cell viability was assessed by MTT assay and expression of Bax, Bcl-2, mTOR, hTERT, PUMA, p53 and p21 genes was analyzed by real-time PCR. Apoptosis and cell cycle were assessed by flow cytometry. Our results revealed that the viability of cells treated with curcumin, metformin, and their combination was significantly (P < 0.05) reduced with increasing the concentration and prolonging the treatment time. Meanwhile, the combination showed a synergistic effect within 48 h. In the curcumin treated group, the expression of Bcl-2 and hTERT genes diminished. In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined. Although all treatments induced apoptosis, the combination of curcumin and metformin showed the maximum level of apoptosis, cytotoxicity, and expression of Bax gene. The combination of curcumin and metformin showed synergistic effects within 48 h. This combination could be a potential therapeutic candidate for prostate cancer to be further investigated.

Comparative evaluation of hydrogen peroxide sporicidal efficacy by different standard test methods.

BACKGROUND AND OBJECTIVES: There are different sporicidal standard tests with various specifications to deal with products that are claimed for sporicidal activity. The aim of this study was to compare the 7% H2O2 sporicidal efficacy against Bacillus subtilis spores using different standard test methods. MATERIALS AND METHODS: The 7% H2O2 sporicidal efficacy against Bacillus subtilis spores was determined according to the AOAC MB-15-04 standard of carrier test and two standard suspension tests (BS EN 13704, AFNOR NF 72-230) in both clean and dirty conditions and by using different interfering substances including bovine serum albumin, yeast extract and skimmed milk. RESULTS: The results of suspension tests with 3 × 105 and 2 × 107 CFU/ml of B. subtilis spore concentration demonstrated that the higher spore counts lead to lower efficacy of 7% H2O2. Also, the sporicidal activity of 7% H2O2 was reduced in the presence of interfering substances. Bovine serum albumin, yeast, and skimmed milk showed similar interfering effects in suspension test with 3 × 105 CFU/ml. While, in suspension tests with higher initial spore count (2 × 107 CFU/ml) severity of interfering effects were intensified and distinct. Our results indicated that the carrier sporicidal test in comparison with suspension tests required more contact time to kill B. subtilis spores. CONCLUSION: The results of this study showed that it is reasonable to use interfering substances and inoculated carriers in accordance with actual conditions of product usage in a sporicidal test. Interfering substances may reduce the contact surface between H2O2 and test spores; therefore, the sporicidal efficacy of H2O2 was diminished. So applying suspension test in clean condition to verify the claim of sporicidal activity is strongly discouraged.

Synergistic anti-tumor effects of Liraglutide, a glucagon-like peptide-1 receptor agonist, along with Docetaxel on LNCaP prostate cancer cell line.

Docetaxel is a first line chemotherapy agent, which stabilizes microtubules in metastatic prostate cancer (PCa). Resistance to Docetaxel and its side effects remain as obstacle for its efficacy in monotherapy. Recently, combination with novel adjuvants have been emerged as a beneficial alternative strategy, which targets multiple important pathways and also requires lower therapeutic dosage, proposing as a strategy to overcome drug resistance. This study investigated whether Liraglutide, a Glucagon Like Peptide-1 Receptor agonist, can reinforce the effect of Docetaxel on LNCaP prostate cancer cell line. Cells were treated by Liraglutide and Docetaxel, alone and in combination. Cytotoxicity was evaluated by MTT assay. Compusyn and Combenefit softwares were used in order to evaluate synergistic efficacy. Apoptosis was determined by Cell cycle analysis and Annexin-V/Propidium iodide staining through flow cytometry. However, the mRNA level of pro-apoptotic gene "Bax" and anti-apoptotic "Bcl-2" were evaluated by quantitative Real-Time PCR. Also, phosphorylation level of ERK1/2 and AKT proteins was investigated by western blotting technique. The results showed that Docetaxel and Liraglutide decreased the viability of LNCaP cells synergistically, caused cell cycle arrest and induced apoptosis potentially. The key proteins' evaluation in ERK/MAPK and AKT/PI3K pathways revealed a significant reduction in phosphorylation level of cells exposed to combination of drugs. Our results suggest that, the combination of Liraglutide and Docetaxel could be considered as a potent strategy in enhancing the efficacy of treatment, decreasing the Docetaxel therapeutic dose and thereby lowering systemic toxicities and resistances.

Preparation of Diphtheria and Pseudomonas Exotoxin A Immunotoxins and Evaluation of Their Cytotoxicity Effect on SK-BR-3, BT-474, and MDA-MB-231 Breast Cancer Cell Lines.

Immunotoxin targeted therapy is a promising way of cancer therapy that is made from a toxin attached to an antibody which target a specific protein presented on cancer cells. In this study, we introduce immunotoxins comprising of truncated pseudomonas exotoxin A (PEA) and diphtheria toxin (DT) conjugated to trastuzumab. The effectiveness of 20 and 30 µg/ml immunotoxins and trastuzumab were studied on SK-BR-3 and BT-474 HER2/neu positive breast cancer cell lines by a cell death assay test. The produced immunotoxins have the potential to reduce the therapeutic dose of the trastuzumab and in the same time achieve higher efficiency.

The relationship between molecular content of mesenchymal stem cells derived exosomes and their potentials: Opening the way for exosomes based therapeutics.

At least, more than half of our understanding of extracellular vesicles owes to the studies conducted over the past few years. When it became clear that the exosomes have various potentials in medicine, extensive research has focused on these potentials in a variety of areas including cancer, drug delivery and regenerative medicine. The growing understanding of molecular structure and functions of exosomes causes the vision to become brighter in the exosomes complexity, and our attitude toward these vesicles has undergone changes accordingly. Proteomic and transcriptomic studies on exosomes have highlighted their molecular diversity. In this review, we explicitly examine the exosomes composition, molecular structure and their therapeutic potentials in some diseases. Due to the very heterogeneous nature of exosomes, the process of their use as a therapeutic agent in the clinic has been challenged. We are still at the beginning of recognizing the molecular composition of exosomes and mechanisms that affect their physiology and biology. The growing trend of engineering of exosomes has shown a promising future to further utilize them in a different field. Molecular profiling of exosomes and their content for their related potentials in regenerative medicine should be done exactly for further defining a minimum content for specific therapeutic potentials.

Thiolated chitosan-lauric acid as a new chitosan derivative: Synthesis, characterization and cytotoxicity.

Chitosan as a biopolymer is an attractive vehicle for biomedical applications due to its unique characteristics. In order to improve chitosan's physicochemical features, chemical modification has been carried out to make it more suitable for such approaches. The aim of this study was to prepare and evaluate thiolated chitosan-lauric acid as a new chitosan derivative for biomedical use. Lauric acid was introduced to chitosan via stable amide bond between carboxylic acid group of fatty acid and the amine in the chitosan and thiolation was carried out using thioglycolic acid. Resulted polymers were characterized by FTIR, 1H NMR and TGA. Moreover, cell viability assessment of new derivative was performed using MTT method. FTIR and 1H NMR results showed that both substitution reactions were successfully completed. Furthermore, new synthesized polymer had no significant cytotoxicity against normal gingiva human cells (HGF1-PI 1).These findings confirm that this new derivative can be introduced as a suitable polymer for biomedical purposes such as mucosal drug delivery.