Construction of recombinant Omp25 or EipB protein loaded PLGA nanovaccines for Brucellosis protection.

Safe and effective vaccine candidates are needed to address the limitations of existing vaccines against Brucellosis, a disease responsible for substantial economic losses in livestock. The present study aimed to encapsulate Omp25 and EipB proteins, knowledged antigen properties, into PLGA nanoparticles, characterize synthesized nanoparticles with different methods, and assessed their in vitro/in vivo immunostimulatory activities to develop new vaccine candidates. The rOmp25 and EipB proteins produced with recombinant DNA technology were encapsulated into PLGA nanoparticles by double emulsion solvent evaporation technique. The nanoparticles were characterized using SEM, Zeta-sizer, and FTIR instruments to determine size, morphology, zeta potentials, and polydispersity index values, as well as to analyze functional groups chemically. Additionally, the release profiles and encapsulation efficiencies were assessed using UV-Vis spectroscopy. After loading with recombinant proteins, O-NPs reached sizes of 221.2±5.21 nm, while E-NPs reached sizes of 274.4±9.51 nm. The cumulative release rates of the antigens, monitored until the end of day 14, were determined to be 90.39% for O-NPs and 56.1% for E-NPs. Following the assessment of the in vitro cytotoxicity and immunostimulatory effects of both proteins and nanoparticles on the J774 murine macrophage cells, in vivo immunization experiments were conducted using concentrations of 16 µg/ml for each protein. Both free antigens and antigen-containing nanoparticles excessively induced humoral immunity by increasing produced Brucella-specific IgG antibody levels for 3 times in contrast to control. Furthermore, it was also demonstrated that vaccine candidates stimulated Th1-mediated cellular immunity as well since they significantly raised IFN-gamma and IL-12 cytokine levels in murine splenocytes rather than IL-4 following to immunization. Additionally, the vaccine candidates conferred higher than 90% protection from the infection according to challenge results. Our findings reveal that PLGA nanoparticles constructed with the encapsulation of recombinant Omp25 or EipB proteins possess great potential to trigger Brucella-specific humoral and cellular immune response.

Tannic Acid Incorporated Antibacterial Polyethylene Glycol Based Hydrogel Sponges for Management of Wound Infections.

Conventional wound dressings fail to provide features that can assist the healing process of chronic wounds. Multifunctional wound dressings address this issue by incorporating attributes including antibacterial and antioxidant activity, and the ability to enhance wound healing. Herein, polyethylene glycol (PEG)-based antibacterial hydrogel sponge dressings are prepared by a rapid and facile gas foaming method based on an acid chloride/alcohol reaction where tannic acid (TA) is included as a reactant to impart antibacterial efficacy as well as to enhance the mechanical properties of the samples. The results reveal that the TA-integrated sponges possess excellent antibacterial properties against both Escherichia coli and Staphylococcus aureus with approximately 6-8 log reduction in the microbial colony count after 6 h, indicating their high potential for management of infection-prone wounds. Compared to the control sample, TA incorporation increases the elastic modulus by twofold. As the samples also exhibit biocompatibility, antioxidant activity, and wound healing capacity, the novel TA-incorporated hydrogels can be an alternative to traditional wound dressings for wounds with low-to-moderate exudate.

Applications of Exosome Vesicles in Different Cancer Types as Biomarkers.

One of the biggest challenges in the fight against cancer is early detection. Early diagnosis is vital, but there are some barriers such as economic, cultural, and personal factors. Considering the disadvantages of radiological imaging techniques or serological analysis methods used in cancer diagnosis, such as being expensive, requiring expertise, and being time-consuming, there is a need to develop faster, more reliable, and cost-effective diagnostic methods for use in cancer diagnosis. Exosomes, which are responsible for intercellular communication with sizes ranging from 30-120 nm, are naturally produced biological nanoparticles. Thanks to the cargo contents they carry, they are a potential biomarker to be used in the diagnosis of cancer. Exosomes, defined as extracellular vesicles of endosomal origin, are effective in cancer growth, progression, metastasis, and drug resistance, and changes in microenvironmental conditions during tumor development change exosome secretion. Due to their high cellular activity, tumor cells produce much higher exosomes than healthy cells. Therefore, it is known that the number of exosomes in body fluids is significantly rich compared to other cells and can act as a stand-alone diagnostic biomarker. Cancer- derived exosomes have received great attention in recent years for the early detection of cancer and the evaluation of therapeutic response. In this article, the content, properties, and differences of exosomes detected in common types of cancer (lung, liver, pancreas, ovaries, breast, colorectal), which are the leading causes of cancer-related deaths, are reviewed. We also discuss the potential utility of exosome contents as a biomarker for early detection, which is known to be important in targeted cancer therapy.

Effect of polycation coating on the long-term pulsatile release of antigenic ESAT-61-20 peptide from PLGA nanoparticles.

The development of novel vaccine formulations against tuberculosis is necessary to reduce the number of new cases worldwide. Polymeric nanoparticles offer great potential as antigen delivery and immunostimulant systems for such purposes. In the study, we have encapsulated the antigenic peptide epitope of ESAT-6 protein of M. tuberculosis into PLGA nanoparticles and coated these nanoparticles with the cationic polymer of quaternized poly(4-vinylpyridine) (QPVP) to obtain a positively charged system as a potential nasal vaccine prototype. The produced spherical nanoparticles had hydrodynamic diameters between 180 and 240 nm with a narrow size distribution. The non-coated nanoparticle exhibited a 3-phase in vitro release profile that was completed in more than 4 months. In this release study, 5% of the peptide was released in the first 6 h and the nanoparticle remained silent until the 70th day. Then, an additional 5% of the peptide was released in 45 days. After coating the nanoparticle with QPVP, the release periods and peptide amounts dramatically changed. The antigenic peptide-loaded nanoparticles coated with the polycation stimulated the macrophages in vitro to release more nitric oxide (NO) compared to the free peptide and non-coated nanoparticle, which reveals the immunostimulant activity of the produced nanoparticle systems. The produced non-coated nanoparticles with the prolonged pulsatile release of the antigenic peptide can be used in the development of single injection self-boosting vaccine formulations. By coating these nanoparticles, both the release profile and immunogenicity can be changed.

The mTOR Signaling Pathway and mTOR Inhibitors in Cancer: Next-generation Inhibitors and Approaches.

mTOR is a serine/threonine kinase that plays various roles in cell growth, proliferation, and metabolism. mTOR signaling in cancer becomes irregular. Therefore, drugs targeting mTOR have been developed. Although mTOR inhibitors rapamycin and rapamycin rapalogs (everolimus, rapamycin, temsirolimus, deforolimus, etc.) and new generation mTOR inhibitors (Rapalink, Dual PI3K/mTOR inhibitors, etc.) are used in cancer treatments, mTOR resistance mechanisms may inhibit the efficacy of these drugs. Therefore, new inhibition approaches are developed. Although these new inhibition approaches have not been widely investigated in cancer treatment, the use of nanoparticles has been evaluated as a new treatment option in a few types of cancer. This review outlines the functions of mTOR in the cancer process, its resistance mechanisms, and the efficiency of mTOR inhibitors in cancer treatment. Furthermore, it discusses the next-generation mTOR inhibitors and inhibition strategies created using nanoparticles. Since mTOR resistance mechanisms prevent the effects of mTOR inhibitors used in cancer treatments, new inhibition strategies should be developed. Inhibition approaches are created using nanoparticles, and one of them offers a promising treatment option with evidence supporting its effectiveness.

Design of a bactericidal hydrogel scaffold containing genipin crosslinked HF-18 peptide.

Wound healing is a process getting affected by internal and external factors and might be interrupted by infections. To overcome infections during wound healing, novel antibacterial agents such as antimicrobial peptides have gained popularity because of the rising antibiotic resistance. Therefore, in this study, a three-dimensional polymeric scaffold was designed for the controlled release of HF-18 peptide, with the contribution of hyaluronic acid, chondroitin sulfate, and chitosan polymers with the crosslinker genipin. The obtained scaffold structure (OPT) was found to have interconnected pores, was pH-responsive and swelled more in acidic conditions (5446.5% at pH: 5.0). It was observed that HF-18-loaded OPT (P-OPT) was able to release HF-18 peptide both in acidic and neutral conditions in a controlled release manner. This study also demonstrated that both OPT and P-OPT were biocompatible and promoted L929 cell attachment and migration. Antimicrobial activity assessments demonstrated that P-OPT was effectively bactericidal on Staphylococcus aureus and methicillin-resistant S. aureus. Moreover, OPT produced a synergistic effect on the antimicrobial activity of HF-18 peptide, as P-OPT showed activity below the reported MIC value. As a result, OPT is considered a promising scaffold as a carrier for HF-18 for wound healing.

Wharton Jelly Derived Mesenchymal Stem Cell's Exosomes Demonstrate Significant Antileishmanial and Wound Healing Effects in Combination with Aloe-Emodin: An in Vitro Study.

The aim of the present study was to explore the antileishmanial performance and wound healing effect of exosomes isolated from Wharton Jelly derived mesenchymal stem cells (WJ-MSCs) in combination with aloe-emodin. MSCs obtained from Wharton Jelly were characterized by flow cytometry. Exosomes were isolated from cultivated stem cells by ultacentrifugation method. Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA) and flow cytometry were used for characterization of obtained exosomes. The cytotoxicities of characterized exosomes and aloe-emodin at different concentrations were investigated on L929 and J774 cell lines. Non-toxic concentrations of each agent were combined and their inhibitory efficacies on L.major promastigotes and amastigotes were investigated by different techniques such as MTT, parasite count and measurements of infection index. Finally, wound healing activities of combinations were examined on in vitro artifical wound model and compared with the use of exosomes alone. According to outcome of flow cytometic analysis, vesicles isolated from WJ-MSCs highly expressed the markers such as CD63 special for exosome profile. SEM and NTA results demonstrated that derived exosomes possessed dimensions between 150 to 200 nanometers and elicited the cup-shape specific to exosomes. Combinations including non-toxic dosages of exosomes and aloe-emodin demonstrated superior antileishmanial effectivenesses both on promastigotes and amastigotes in contrast to use of exosome alone since they lead to inhibition of promastigotes and amastigotes for 4 and 10-folds in comparison to control, respectively. Additionally, combinations elicited more rapidly and effective in vitro wound-healing performance in contrast to use of exosome alone. At the end of 24 h incubation application of combinations gave rise to wound closure at a rate of 72 %, while in the control group 52 % of wound area has not been healed, yet. These results reflect that mentioned combination has great potential to be used in treatment of cutaneus leishmaniasis (CL) since they have magnificient capacity to inhibit Leishmania parasites while enhancing wound healing.

Preparation and Characterization of Graphene-Based 3D Biohybrid Hydrogel Bioink for Peripheral Neuroengineering.

Peripheral neuropathies can occur as a result of axonal damage, and occasionally due to demyelinating diseases. Peripheral nerve damage is a global problem that occurs in 1.5%-5% of emergency patients and may lead to significant job losses. Today, tissue engineering-based approaches, consisting of scaffolds, appropriate cell lines, and biosignals, have become more applicable with the development of three-dimensional (3D) bioprinting technologies. The combination of various hydrogel biomaterials with stem cells, exosomes, or bio-signaling molecules is frequently studied to overcome the existing problems in peripheral nerve regeneration. Accordingly, the production of injectable systems, such as hydrogels, or implantable conduit structures formed by various bioprinting methods has gained importance in peripheral neuro-engineering. Under normal conditions, stem cells are the regenerative cells of the body, and their number and functions do not decrease with time to protect their populations; these are not specialized cells but can differentiate upon appropriate stimulation in response to injury. The stem cell system is under the influence of its microenvironment, called the stem cell niche. In peripheral nerve injuries, especially in neurotmesis, this microenvironment cannot be fully rescued even after surgically binding severed nerve endings together. The composite biomaterials and combined cellular therapies approach increases the functionality and applicability of materials in terms of various properties such as biodegradability, biocompatibility, and processability. Accordingly, this study aims to demonstrate the preparation and use of graphene-based biohybrid hydrogel patterning and to examine the differentiation efficiency of stem cells into nerve cells, which can be an effective solution in nerve regeneration.

Formulating and Characterizing an Exosome-based Dopamine Carrier System.

Exosomes between 40 and 200 nm in size constitute the smallest subgroup of extracellular vesicles. These bioactive vesicles secreted by cells play an active role in intercellular cargo and communication. Exosomes are mostly found in body fluids such as plasma, cerebrospinal fluid, urine, saliva, amniotic fluid, colostrum, breast milk, joint fluid, semen, and pleural acid. Considering the size of exosomes, it is thought that they may play an important role in central nervous system diseases because they can pass through the blood-brain barrier (BBB). Hence, this study aimed to develop an exosome-based nanocarrier system by encapsulating dopamine into exosomes isolated from Wharton's jelly mesenchymal stem cells (WJ-MSCs). Exosomes that passed the characterization process were incubated with dopamine. The dopamine-loaded exosomes were recharacterized at the end of incubation. Dopamine-loaded exosomes were investigated in drug release and cytotoxicity assays. The results showed that dopamine could be successfully encapsulated within the exosomes and that the dopamine-loaded exosomes did not affect fibroblast viability.

Polymeric Approach to Adjuvant System in Antibody Production against Leishmaniasis Based on Hybridoma Technology.

Background: Leishmaniasis is a zoonotic disease, which is one of the serious public health problems in the world. Nowadays, antibody production using hybridoma technology may be a correct approach in terms of sensitivity in the diagnosis of diseases such as leishmaniasis. The aim of this study was investigation of the effectiveness of different adjuvants on polyclonal antibody production against L. tropica based on hybridoma technique. Methods: Accordingly, Freund's adjuvant (1956, M. tuberculosis), as a classic adjuvant in studies, was used comparatively with the non-toxic polymeric based Polyoxidonium adjuvant. All animal immunization procedures were conducted at Bezm-i Alem University Experimental Animal Research Center. The adjuvant response was tested both in the serum sample and in the antibodies produced by the hybridomas. The antibody titers were determined with ELISA. Results: Freund's and Polyoxidonium (PO) group blood titer's increased approximately 5.5 fold compared to control after the 6th and 8th immunization. Hybridomas produced from mice immunized with PO adjuvant induced only antigen-specific antibody response and did not develop an immune response against the adjuvant. Conclusion: Adjuvant selection is very important in terms of the specificity of antibody responses of cells produced in hybridoma technology. Therefore, PO is recommended as a new adjuvant system in this study.

Nano-co-delivery of lipophosphoglycan with soluble and autoclaved leishmania antigens into PLGA nanoparticles: Evaluation of in vitro and in vivo immunostimulatory effects against visceral leishmaniasis.

The aim of the present study was to encapsulate lipophosphoglycan molecule (LPG) which is one of the most immunogenic antigens of Leishmania parasites into PLGA nanoparticles with autoclaved or soluble leishmanial antigens, characterize synthetized nanoparticles with different methods and evaluate their in vitro/in vivo immunostimulatory activities to develop new vaccine candidates. PLGA nanoparticles including LPG and autoclaved leishmania antigen (ALA) or soluble leishmania antigen (ALA) were synthetized by double emulsion solvent evaporation method. The synthetized nanoparticles were characterized by SEM and Zeta-sizer instruments for determination of size, zeta potentials and polydispersity index (PDI) values. The antigen release profiles and encapsulation efficiencies were determined by UV-Vis spectroscopy. Griess reaction and ELISA tests were used for measurements of produced nitric oxide (NO) and cytokine levels of macrophages and splenocytes treated with nanoparticles. For determination of protective effects of nanoparticles, parasite reduction in livers and spleens of immunized mice were calculated by LDU values post-infection. According to results, (SLA-LPG) PLGA NPs and (ALA-LPG) PLGA NPs possessed the sizes of 253 and 307 nm respectively. Antigen-loaded nanoparticles elevated the released NO amounts from macrophages for 14 and 18-folds in contrast to control. Furthermore, synthetized nanoparticles significantly triggered macrophages to produce excessive levels of IFN-γ and IL-12 cytokines. Besides it was detected that vaccination of mice with (SLA-LPG) PLGA NPs and (ALA-LPG) PLGA NPs elicited approximately 80% protection from Visceral Leishmaniasis. Furthermore, (SLA-LPG) PLGA NPs and (ALA-LPG) PLGA NPs lead to 10 to 14-folds increase in secreted Th1 cytokine levels from splenocytes than control demonstrating abundantly stimulation of T cell response following to vaccination with nano-vaccine formulations. These results reveal that both (SLA-LPG) PLGA NPs and (ALA-LPG) PLGA NPs have excellent immunostimulatory activities and they are promising nanovaccine formulations for the prevention of leishmaniasis in near future.

An insight into the epitope-based peptide vaccine design strategy and studies against COVID-19.

SARS-CoV-2 is a new member of the coronavirus family and caused the pandemic of coronavirus disease 2019 (COVID-19) in 2020. It is crucial to design and produce an effective vaccine for the prevention of rapid transmission and possible deaths wcaused by the disease. Although intensive work and research are being carried out all over the world to develop a vaccine, an effective and approved formulation that can prevent the infection and limit the outbreak has not been announced yet. Among all types of vaccines, epitope-based peptide vaccines outshine with their low-cost production, easy modification in the structure, and safety. In this review, vaccine studies against COVID-19 have been summarized and detailed information about the epitope-based peptide vaccines against COVID-19 has been provided. We have not only compared the peptide vaccine with other types of vaccines but also presented comprehensive literature information about development steps for an effective and protective formulation to give an insight into on-going peptide vaccine studies against SARS-CoV-2.

Resuscitation of the Helicobacter pylori Coccoid Forms by Resuscitation Promoter Factor Obtained from Micrococcus Luteus.

Helicobacter pylori is a gram negative, spiral-shaped, and microaerophilic bacteria which can cause life-threatening diseases. It is known that more than 55% of the human population in the world is already infected by this bacterium. The traditional treatment of H. pylori infection consists of a combination of two or more antibiotics. However, H. pylori has evolved to turning its shape from spiral to coccoid form in the presence of antibiotics and this decreases the therapeutic efficacies of conventional antibiotic applications. Resuscitation promoter factor (RPF) is a protein secreted by Micrococcus luteus have significant resuscitation effects on some bacteria especially in the group of viable but non-culturable (VBNC) pathogens. However, there is no study in the literature investigating the resuscitation effects of RPF derived from M. luteus on H. pylori in order to change its form from coccoid to spiral. The purpose of this study is to investigate the resuscitation effect of RPF-containing metabolites isolated from M. luteus on the morphological transformation of H. pylori coccoid forms to spiral forms in order to increase their susceptibilities to antibiotic treatments. Rpf-containing metabolites were primarily obtained from M. luteus culture supernatants. H. pylori was exposed to five different conditions such as prolonged culture, incubation at + 4 °C, incubation at + 22 °C, cultivation in PBS and treatment with kanamycin in order to induce transformations of bacteria to coccoid forms. Induced H.pylori coccoids were characterized by inverted microscope, UV spectrophotometer, SEM imaging, and flow-cytometer. As a result, it was found that the most suitable condition for inducing coccoid forms was cultivation of bacteria with kanamycin. Followingly, different concentrations of RPF-containing metabolites were applied on H. pylori coccoids induced by kanamycin. For the first time in this study, it was determined that the Rpf-containing metabolites obtained from M. luteus demonstrated very high resuscitation effect on kanamycin-induced H. pylori coccoid forms. This new approach for resuscitation of H. pylori coccoids is thought to play an important role in increasing the treatment effectiveness of the conventional antibiotics against the infection.

A nanotechnology-based new approach in the treatment of breast cancer: Biosynthesized silver nanoparticles using Cuminum cyminum L. seed extract.

The present study reports the anticancer activities of Cuminum cyminum L. (Cumin) seed extract, chemically synthetized silver nanoparticles (AgNPs) and biosynthesized silver nanoparticles (Bio-AgNPs) from Cumin seeds on human breast adenocarcinoma cell line (MCF-7) and human breast adenocarcinoma metastatic cell line (AU565). The synthetized nanoparticles were characterized by dynamic light scattering (DLS), UV-visible spectroscopy (UV-Vis), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and Scanning electron microscopy (SEM). The cytotoxic and anticancer effects of AgNPs and Bio-AgNPs were determined by MTT assay. According to the cytotoxicity analysis, Bio-AgNPs appears to be less toxic against J774 macrophage cells than AgNPs since IC50 values were measured as 0.75 and 1.25 µg/ml for AgNPs and Bio-AgNPs, respectively. On the other hand, Bio-AgNPs demonstrated significant inhibitory effects on human breast cancer cells at non-toxic concentrations such as 0.25 and 0.5 µg/ml. However, at increased concentrations, the lethal effects of AgNPs on breast cancer cells were higher than Bio-AgNPs. When cytotoxic and anticancer characteristics of Cumin extract were investigated, it was established that it did not show any inhibitory effect on J774 cells, while killing the half of MCF-7 cells at investigated concentrations. Interestingly, Cumin extract gave rise to no inhibitory effects against AU565 cells. On the other hand, AgNPs and Bio-AgNPs exhibited considerable anticancer activities on both cell lines. The inhibition percentages of AgNPs on MCF-7 and AU565 cell lines were respectively evaluated as 95% and 97% at the highest concentrations applied (12.5 µg/ml). Similarly, we determined that 87.5% and 96% of MCF-7 and AU565 cells were respectively inhibited when they were exposed to the highest concentrations of Bio-AgNPs. Considering relatively toxic-free features of Bio-AgNPs prepared from Cuminum cyminum L. seed extracts, it can be thought that this formulation will be a pioneer in development of nanotechnology-based new anticancer drug for the treatment of breast cancer in near future.

Investigation of antileshmanial activities of Cuminum cyminum based green silver nanoparticles on L. tropica promastigotes and amastigotes in vitro.

Leishmaniasis is one of the most important parasitic diseases, which is caused by Leishmania species. Nowadays; although pentavalent antimonials are used as the basic treatment option for Cutaneous Leishmaniasis, high cost, toxicity and resistance of the parasites to the medication over time are some important limitations causing several problems in the treatment. In recent years, the progress in the field of green nanotechnology provides the development of green nanoparticle-based treatment methods for Cutaneous Leishmaniasis. The importance of green nanoparticles has gradually increased due to their special reductive, stabilizing, antioxidant and non-toxic properties. Although there are many studies based on green nanoparticles against Leishmania parasites, we have not found any research about antileishmanial activities of biosynthesized silver nanoparticles (Bio-AgNPs) using Cuminum cyminum L (Cumin) seed extract. Therefore for the first time in this study in vitro antileishmanial effects of Bio-AgNPs prepared from Cumin seed extract were examined on L. tropica promastigote and amastigote forms and their efficacies were compared with chemically synthetized AgNPs. During the experiments, antileishmanial effects of synthetized nanoparticles were determined on both promastigote and amastigote forms of Leishmania parasites by detecting different parameters such as proliferation, infection index and produced nitric oxide (NO) amounts from macrophages. According to the results, it was shown that Bio-AgNPs and AgNPs excessively inhibited L. tropica promastigotes and amastigotes by significantly decreasing proliferation rates of promastigotes and metabolic activities of amastigotes, as well. Moreover, infection index rates of macrophages revealed remarkable anti-amastigote performances of Bio-AgNPs. Besides, Bio-AgNPs stimulated macrophages to release NO to kill Leishmania parasites. Consequently, for the first time, Bio-AgNPs were found to be more effective on both forms of Leishmania parasites than AgNPs. Obtained results indicated high antileishmanial potential of green nanoparticles on L. tropica parasites, causative agents of Cutaneous Leishmaniasis. Thus, obtained results demonstrated that green nanoparticles can lead to the development of new, safer, stable and more effective antileishmanial formulations against Cutaneous Leishmaniasis.

Current Approaches in Treatment of Diabetic Retinopathy and Future Perspectives.

Diabetes mellitus (DM) is a metabolic disease, which is the most common cause of low vision in developing countries and affects almost all systems of the body. In view of the increase in DM prevalence in the world, it would not be a surprise that diabetic retinopathy (DR) and other vascular complications related to diabetes become a serious public health problem. Currently, vascular endothelial growth factor, laser photocoagulation, and intravitreal steroids are the mainstays for DR treatment, but the efficacy of these treatment strategies remains insufficient. Therefore, new treatment modalities for DR have been developed, such as stem cell therapies, extracellular vesicular system, and nanodrug delivery systems. Although there have been several reviews in the literature on the treatment of DR, we have not confronted any review that has the titles of all these topics. With this review, we aim to present the pathophysiology of DR and to review the current and promising new treatment methods based on stem cells, extracellular vesicular system, and nanodrug delivery systems for the future of DR management.

An overview of nanotechnology-based treatment approaches against Helicobacter Pylori.

Introduction: Helicobacter Pylori (H.Pylori) is a pathogen that infects about 50% of the world's population and is known to be responsible for gastroduodenal diseases such as atrophic gastritis, peptic ulcer and stomach cancer. Nowadays, there is no treatment that ensures complete eradication. In addition, resistance to antibiotics used in the current treatment adversely affects the success rates in the fight against infection. Areas covered: This article take attention to treatment approaches using nanoparticles as an alternative to H.Pylori treatment to cope with increased antibiotic resistance. The purpose of this review is to provide an overview of the current limitations and new promising altenatives in treatment of H.Pylori, to highlight the location of nanotechnology to overcome treatment failures, and to emphasize the advantages of using membrane-coated nanoparticles for the first time. Expert opinion: Because of the current problems in the treatment of H.Pylori, there is increasing interest in alternative approaches including nanotechnology. The strong antibacterial effects of metallic nanoparticles, the advantages of polymeric nanoparticles in drug delivery and drug protection, and the prominent properties of membrane-coated nanoparticles in direct targeting demonstrate the significance of nanotechnology in developing new approaches for treatment of H.Pylori infection.

Current aspects in treatment of breast cancer based of nanodrug delivery systems and future prospects.

Breast cancer is one of the most common diseases worldwide. The risk of getting this disease in female is 30% and the mortality rate is 14%. The breast cancer treatment is based on surgery, chemotherapy and radiotherapy. However, an effective treatment method has not been developed. The main cause of failure in the treatment is cancer stem cells metastasis and chemo-resistance. The use of nanocarrier systems against breast cancer stem cells has great importance. Not only advantages of polymeric drug delivery systems are increasing the stability and reduce the side effects of drugs, but also they have disadvantages such as biocompatibility and long-term potential safety. However, in recent years, studies on exosomes provide several advantages. Exosomes usage as nanocarrier do not cause immunological reactions also the drug effectively transport into the cytosol of targeted cell and have more stability characteristics. Although there are studies about various nanocarrier systems in literature against breast cancer but in general, we have not found any review that brings them together and develops a systematic approach to solving the problem. This review mentions prospective new strategies based on various nanocarrier systems and emphasize the importance of exosome based on drug delivery systems in the treatment of breast cancer.

Problems in Stem Cell Therapy for Cardiac Repair and Tissue Engineering Approaches Based on Graphene and Its Derivatives.

BACKGROUND: Today, coronary artery disease is still one of the most important causes of mortality despite advanced surgical methods, pharmacotherapies and organ transplantation. These treatment modalities are intended to prevent further progression of myocardial infarction and do not involve the repair of the damaged part. Therefore, stem cell therapy has emerged as a new approach for the treatment of coronary artery disease. However, there are some restrictions that limit the use of these cells for desired repair. The leading limitation is that newly formed cardiomyocytes do not provide electrical integrity with local cells. OBJECTIVE: In this paper, we review the difficulties that limit the use of stem cell therapy in cardiac repair and emphasize the importance of the integration of stem cell with tissue scaffolds with conductivity. Furthermore, significance of using graphene scaffolds in cardiac tissue engineering is highlighted due to its conductivity features. RESULT: Recently, the fabrication of tissue scaffoldings has made it possible to create a biomimetic cellular environment while providing a new approach to solving these problems in treatment. Especially, the integration of stem cell therapy with graphene-based tissue scaffolds with electrical conductivity, is one of the promising new strategies to turn the success of two approaches of tissue engineering into synergistic effect in cardiac repair. CONCLUSION: Literature analysis has demonstrated that there are some limitations in use of stem cell therapy for successful treatment of cardiac repair and graphene-based tissue engineering approaches which are promising to solve these problems in the near future.

Comparative study on the antileishmanial activities of chemically and biologically synthesized silver nanoparticles (AgNPs).

The present study was conducted to investigate the antileishmanial activity of biogenic silver nanoparticles (AgNPs) compared to chemically synthesized AgNPs. A nano dimension size (10-15 nm) biogenic AgNPs was produced and characterized by UV-Vis spectroscopy and X-rays diffraction. The chemically synthesized AgNPs was recovering from our previous study with a nanoparticle (NP) size in the range of 10-40 nm. The antileishmanial activities were investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assay. The infectivity was determined by Giemsa staining of the infected macrophages cells. Nitric oxide (NO) accumulation was measured by Griess reagent using NaNO2 as a positive control. After 24 h of exposure with nanoparticles (NPs), a concentration-dependent growth inhibition was observed. The IC50 values were determined against promastigotes of L. infantum as 19.42 ± 2.76 µg/ml for leaves aqueous extract mediated AgNPs, 30.71 ± 1.91 µg/ml for stem mediated AgNPs and 51.23 ± 2.20 µg/ml for chemically synthesized AgNPs. It was also detected that all types of NPs produced NO at a significant level. However, the production of a high-level of NO in the biologically synthesized NPs activated macrophage cells, infected with L. infantum promastigotes indicates that NO radicals are mainly responsible for induced cell death and a decrease in the pathogenicity of the parasites. Since, biogenic nanoparticles are cost-effective, eco-friendly, simple to synthesize, and more effective than chemically synthesized silver nanoparticles, therefore, it could be used as a potential alternative for the development of antileishmanial drugs.