Introduction of a new recombinant vaccine based on GRP78 for breast cancer immunotherapy and evaluation in a mouse model.

Introduction: Breast cancer is one of the most prevalent malignancies in women. Several treatment options are available today, including surgery, chemotherapy, and radiotherapy. Immunotherapy, as a highly specific therapy, involves adaptive immune responses and immunological memory. In our present research, we used the recombinant C-terminal domain of the GRP78 (glucose- regulated protein 78) protein to induce an immune response and investigate its therapeutic impact in the 4T1 breast cancer model. Methods: BALB/c mice were immunized with the cGRP78 protein. The humoral immune response was assessed by ELISA. Then, BALB/c mice were injected subcutaneously with 1×106 4T1 tumor cells. Subsequently, tumor size and survival rate measurements, MTT, and cytokine assays were performed. Results: The animals receiving the cGRP78 vaccine showed significantly more favorable survival and slower tumor growth rates compared with unvaccinated tumor-bearing mice as the negative control mice. Circulating levels of tumoricidal cytokines such as IFNγ were higher, whereas tolerogenic cytokines such as IL-2, 6, and 10 either did not increase or had a decreasing trend in mice receiving cGRP78. Conclusion: cGRP78 vaccines generated potent immunotherapeutic effects in a breast cancer mouse model. This novel strategy of targeting the GRP78 protein can promote the development of cancer vaccines and immunotherapies for breast cancer malignancies.

Targeted drug delivery using nanobodies to deliver effective molecules to breast cancer cells: the most attractive application of nanobodies.

Targeted drug delivery is one of the attractive ways in which cancer treatment can significantly reduce side effects. In the last two decades, the use of antibodies as a tool for accurate detection of cancer has been noted. On the other hand, the binding of drugs and carriers containing drugs to the specific antibodies of cancer cells can specifically target only these cells. However, the use of whole antibodies brings challenges, including their large size, the complexity of conjugation, the high cost of production, and the creation of immunogenic reactions in the body. The use of nanobodies, or VHHs, which are a small part of camel heavy chain antibodies, is very popular due to their small size, high craftsmanship, and low production cost. In this article, in addition to a brief overview of the structure and characteristics of nanobodies, the use of this molecule in the targeted drug delivery of breast cancer has been reviewed.

Polymeric nanoparticles for DNA vaccine-based cancer immunotherapy: a review.

Cancer is one of the leading causes of death and mortality in the world. There is an essential need to develop new drugs or therapeutic approaches to manage treatment-resistant cancers. Cancer immunotherapy is a type of cancer treatment that uses the power of the body's immune system to prevent, control, and eliminate cancer. One of the materials used as a vaccine in immunotherapy is DNA. The application of polymeric nanoparticles as carriers for DNA vaccines could be an effective therapeutic approach to activate immune responses and increase antigen presentation efficiency. Various materials have been used as polymeric nanoparticles, including: chitosan, poly (lactic-co-glycolic acid), Polyethylenimine, dendrimers, polypeptides, and polyesters. Application of these polymer nanoparticles has several advantages, including increased vaccine delivery, enhanced antigen presentation, adjuvant effects, and more sustainable induction of the immune system. Besides many clinical trials and commercial products that were developed based on polymer nanoparticles, there is still a need for more comprehensive studies to increase the DNA vaccine efficiency in cancer immunotherapy using this type of carrier.

Covid-19 prevention and treatment by targeting Fc-fusion proteins: An experience to fight emerging diseases.

The coronavirus disease 2019 (Covid-19) pandemic has been considered a major threat to human health. Effective therapeutic approaches are urgently required. Spike protein and the Angiotensin-converting enzyme 2 (ACE2) receptors have critical roles in SARS-CoV-2 infection. As a result, these two proteins are considered potential targets for the development of a wide variety of biotherapeutics and vaccines for controlling Covid-19. The fusion proteins have desirable medicinal properties, including high serum half-life, stability, and solubility in the body. Moreover, other Fc-fusion proteins used to treat other diseases have no known side effects. These Fc-fusion proteins are valuable biopharmaceuticals and have been proposed as therapeutic candidates for the treatment and prevention of Covid-19 owing to their potential therapeutic benefits.

The recent advancements in the early detection of cancer biomarkers by DNAzyme-assisted aptasensors.

Clinical diagnostics rely heavily on the detection and quantification of cancer biomarkers. The rapid detection of cancer-specific biomarkers is of great importance in the early diagnosis of cancers and plays a crucial role in the subsequent treatments. There are several different detection techniques available today for detecting cancer biomarkers. Because of target-related conformational alterations, high stability, and target variety, aptamers have received considerable interest as a biosensing system component. To date, several sensitivity-enhancement strategies have been used with a broad spectrum of nanomaterials and nanoparticles (NPs) to improve the limit and sensitivity of analyte detection in the construction of innovative aptasensors. The present article aims to outline the research developments on the potential of DNAzymes-based aptasensors for cancer biomarker detection.

Analysis and comparison of anti-RBD neutralizing antibodies from AZD-1222, Sputnik V, Sinopharm and Covaxin vaccines and its relationship with gender among health care workers.

BACKGROUND: Vaccine efficiency has a significant role in the public perception of vaccination. The current study was designed to evaluate the efficacy of COVID-19 vaccines (AZD-1222, Sputnik-V, Sinopharm, and Covaxin) and the effect of gender on vaccine efficacy. We evaluated the efficacy of these vaccines among 214 health care employees in Iran. Blood samples were taken from all participants on day 0 and 14 days after the second dose. Humoral responses were evaluated by the PT-SARS-CoV-2-Neutralizing-Ab-96. RESULTS: The frequency of immunized individuals in the Sputnik V and AZD-1222 groups was 91% and 86%, respectively. This rate was 61% and 67% for Sinopharm and Covaxin vaccines. A comparison of the results obtained from the effectiveness of the vaccines between female and male groups did not demonstrate a significant difference. CONCLUSION: According to the results, Sputnik V and AZD-1222 vaccines were more effective than Sinopharm and Covaxin vaccines. Moreover, the effectiveness of these vaccines is not related to gender.

In silico and in vitro analysis of a rational mutation in gIII signal peptide and its effects on periplasmic expression of rhGH in E. coli.

The secretion efficiency of a heterologous protein in E. coli is mainly dictated by the N-terminal signal peptide fused to the desired protein. In this study, we aimed to select and introduce mutations into the - 1, - 2 and - 3 positions of the gIII signal peptide (originated from filamentous phage fd Gene III) fused to the N-terminus of the human growth hormone (hGH), and study its effect on the secretion efficiency of the recombinant hGH into the periplasmic space of E. coli Top10. Bioinformatics software such as SignalP-5.0 and PrediSi were employed to predict the effects of the mutations on the secretion efficiency of the recombinant hGH. Site-directed mutagenesis was applied to introduce the desired mutations into the C-terminus of the gIII signal peptide. The periplasmic expression and the secretion efficiency of the recombinant hGH using the native and mutant gIII signal peptides were compared in E. coli Top10 under the control of araBAD promoter. Our results from bioinformatics analysis indicated that the mutant gIII signal peptide was more potent than the native one for secretion of the recombinant hGH in E. coli. While our experimental results revealed that the mutation had no effect on hGH secretion. This result points to the importance of experimental validation of bioinformatics predictions.

Nanobodies; new molecular instruments with special specifications for targeting, diagnosis and treatment of triple-negative breast cancer.

Breast cancer is the most common type of cancer in women and the second leading cause of cancer death in female. Triple-negative breast cancer has a more aggressive proliferation and a poorer clinical diagnosis than other breast cancers. The most common treatments for TNBC are chemotherapy, surgical removal, and radiation therapy, which impose many side effects and costs on patients. Nanobodies have superior advantages, which makes them attractive for use in therapeutic agents and diagnostic kits. There are numerous techniques suggested by investigators for early detection of breast cancer. Nevertheless, there are fewer molecular diagnostic methods in the case of TNBC due to the lack of expression of famous breast cancer antigens in TNBC. Although conventional antibodies have a high ability to detect tumor cell markers, their large size, instability, and costly production cause a lot of problems. Since the HER-2 do not express in TNBC diagnosis, the production of nanobodies for the diagnosis and treatment of cancer cells should be performed against other antigens expressed in TNBC. In this review, nanobodies which developed against triple negative breast cancer, were classified based on type of antigen.

The Recent Progress in DNAzymes-Based Aptasensors for Thrombin Detection.

Thrombin (TB) is classified among human blood coagulation proteins with key functions in hemostasis of blood vessels, wound healing, atherosclerosis, tissue adhesion, etc. Moreover, TB is involved as the main enzyme in the conversion of the fibrinogen to fibrin. Given the importance of TB detection in the clinical area, the development of innovative methods can considerably improve TB detection. Newly, aptasensors or aptamer-based biosensors have received special attention for sensitive and facile TB detection. In addition, the aptamer/nanomaterial conjugates have presented new prospects in accurate TB detection as nanoaptasensors. DNA-based enzymes or DNAzymes, as new biocatalysts, have many advantages over protein enzymes and can be used in analytical tools. This article reviews a brief overview of significant progresses regarding the various types of DNAzymes-based aptasensors and nano aptasensors developed for thrombin detection. In the following, challenges and prospects of TB detection by DNAzymes-based aptasensors are discussed.

Outlook of therapeutic and diagnostic competency of nanobodies against SARS-CoV-2: A systematic review.

PURPOSE: The newly emerged coronavirus (SARS-CoV-2) continues to infect humans, and no completely efficient treatment has yet been found. Antibody therapy is one way to control infection caused by COVID-19, but the use of classical antibodies has many disadvantages. Heavy chain antibodies (HCAbs) are single-domain antibodies derived from the Camelidae family. The variable part of these antibodies (Nanobodies or VHH) has interesting properties such as small size, identify criptic epitopes, stability in harsh conditions, good tissue permeability and cost-effective production causing nanobodies have become a good candidate in the treatment and diagnosis of viral infections. METHODS: Totally 157 records (up to November 10, 2021), were recognized to be reviewed in this study. 62 studies were removed after first step screening due to their deviation from inclusion criteria. The remaining 95 studies were reviewed in details. After removing articles that were not in the study area, 45 remaining studies met the inclusion criteria and were qualified to be included in the systematic review. RESULTS: In this systematic review, the application of nanobodies in the treatment and detection of COVID-19 infection was reviewed. The results of this study showed that extensive and sufficient studies have been performed in the field of production of nanobodies against SARS-CoV-2 virus and the obtained nanobodies have a great potential for use in patients infected with SARS-CoV-2 virus. CONCLUSION: According to the obtained results, it was found that nanobodies can be used effectively in the treatment and diagnosis of SARS-CoV-2 virus.

A Comprehensive Review on Selenium and Its Effects on Human Health and Distribution in Middle Eastern Countries.

Selenium (Se) is an important microelement with numerous positive effects on human health and diseases. It is important to specify that the status and consumption of Se are for a specific community as the levels of Se are extremely unpredictable between different populations and regions. Our existing paper was based on the impacts of Se on human health and disease along with data on the Se levels in Middle Eastern countries. Overall, the findings of this comprehensive review show that the consumption and levels of Se are inadequate in Middle Eastern nations. Such findings, together with the growing awareness of the importance of Se to general health, require further work primarily on creating an acceptable range of blood Se concentration or other measures to determine optimal Se consumption and, consequently, to guarantee adequate Se supplementation in populations at high risk of low Se intake.

Prevalence of COVID-19 vaccines (Sputnik V, AZD-1222, and Covaxin) side effects among healthcare workers in Birjand city, Iran.

BACKGROUND: The prevalence of vaccine side effects plays an important role in public perception about vaccination programs. This study was designed to investigate the side effects of the first dose of COVID-19 vaccine; Sputnik-V, AZD-1222, and Covaxin. METHODS: A study was performed to evaluate the side effects of these vaccine among 503 health care workers in Birjand (Iran). Our study used the questionnaire consisted of 4 main categories including demographic data, previous COVID-19 infection, vaccine information, and local and systemic side effects of vaccines. RESULTS: 81.9%, 88.8%, and 92.9% of people who have been vaccinated with Sputnik-V, AZD1222, and Covaxin vaccines, respectively, have reported at least one side effect. The prevalence of systemic side effects in AZD-1222 vaccine was higher than Sputnik V and Covaxin vaccines. Injection site pain (62.1%), fatigue (43.9%), muscle pain (42.5%), and fever (40.6%) were the most common side effects in all three vaccines. Side effect frequency was higher in the female group (90.6%) than the male group (79.5%). The prevalence of side effects with Sputnik V and Covaxin vaccines was reduced in the elderly. Moreover, the prevalence of side effects was higher in the case of convalescent patients (92.4 %) than in the group with no history of infection. The prevalence of side effects was higher in person with a BMI above 25 in the AZD-1222 and Covaxin vaccines. CONCLUSIONS: The most common side effects of the Sputnik-V, AZD-1222, and Covaxin vaccine among Birjand (Iran) healthcare workers were injection site pain, muscle pain, fatigue, fever, and headache. Age and gender were the most important variables in the prevalence of vaccine side effects.

Nanobodies: a tool to open new horizons in diagnosis and treatment of prostate cancer.

BACKGROUND: Prostate cancer is one of the most common cancers in men and its incidence has increased dramatically in the last decade. This increase in the detection of this type of cancer is based more on the detection of PSA or PSMA antigens as the most important specific antigens of this cancer, and this early detection has greatly helped in the more optimal treatment of patients. MAIN BODY: Many methods have been proposed by researchers for early detection of prostate cancer, but most of the methods used today to detect this type of cancer have been using classical antibodies. Although classical antibodies are able to detect tumor cell markers, but instability, large size, costly and laborious production, and random immobility characteristics, causes many problems. Nanobodies or VHHs, which are derived from camel heavy chain antibodies, have special advantages and have eliminated the disadvantages of classical antibodies which makes them attractive to use in biosensors and cancer diagnostic kits. The research that has been done so far shows that the introduced nanobodies are created for the purpose of targeting, detecting and sensing prostate cancer cells with two main purposes. The first is the efficient identification of prostate cancer and the second is the elimination of cancer cells. CONCLUSION: Research shows the use of specific nanobodies against prostate cancer antigens in the design of biosensors and target therapy will be very interesting. In this review article, these nanobodies are introduced and categorized based on their performance.

Application of mesenchymal stem cells in corneal regeneration.

Due to delicate its structure, the cornea is susceptible to physical, chemical, and genetic damages. Corneal transplantation is the main treatment for serious corneal damage, but it faces significant challenges, including donor shortages and severe complications. In recent years, cell therapy is suggested as a novel alternative method for corneal regeneration. Regarding the unique characteristics of Mesenchymal stem cells including the potential to differentiate into discrete cell types, secretion of growth factors, mobilization potency, and availability from different sources; special attention has been paid to these cells in corneal engineering. Differentiation of MSCs into specialized corneal cells such as keratocytes, epithelial and endothelial cells is reported. Potential for Treatment of keratitis, reducing inflammation, and inhibition of neovascularization by MSCs, introducing them as novel agents for corneal repairing. In this review, various types of MSCs used to treat corneal injuries as well as their potential for restoring different corneal layers was investigated.

Emerging Technologies for the Treatment of COVID-19.

The new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), turned into a pandemic affecting more than 200 countries. Due to the high rate of transmission and mortality, finding specific and effective treatment options for this infection is currently of urgent importance. Emerging technologies have created a promising platform for developing novel treatment options for various viral diseases such as the SARS-CoV-2 virus. Here, we have described potential novel therapeutic options based on the structure and pathophysiological mechanism of the SARS-CoV-2 virus, as well as the results of previous studies on similar viruses such as SARS and MERS. Many of these approaches can be used for controlling viral infection by reducing the viral damage or by increasing the potency of the host response. Owing to their high sensitivity, specificity, and reproducibility, siRNAs, aptamers, nanobodies, neutralizing antibodies, and different types of peptides can be used for interference with viral replication or for blocking internalization. Receptor agonists and interferon-inducing agents are also potential options to balance and enhance the innate immune response against SARS-CoV-2. Solid evidence on the efficacy and safety of such novel technologies is yet to be established although many well-designed clinical trials are underway to address these issues.

Nanobodies, the potent agents to detect and treat the Coronavirus infections: A systematic review.

The newly emerged coronavirus (SARS-CoV-2) continues to infect humans, and no effective treatment has yet been found. Antibody therapy is one way to control infection caused by COVID-19. However, the use of classical antibodies raises complex issues. Heavy chain antibodies (HCAbs) are single-domain antibodies derived from the Camelidae family. The variable part of these antibodies (Nanobodies or VHH) has interesting properties such as small size, cost-effective production, and good tissue permeability, causing VHH to be regarded as an antiviral therapeutics. However, the small size of nanobodies may lead to low antigen binding affinity and rapid renal clearance. In this systematic review, the application of nanobodies in the treatment of COVID-19 infection and other similar infections (MERS and SARS) was reviewed.

Isolation of Indigenous Selenium Tolerant Yeast and Investigation of the Relationship Between Growth and Selenium Biotransformation.

Purpose: Organic selenium compound such as selenomethionine plays a significant function in the response to oxidative stress. Saccharomyces cerevisiae have the ability to accumulate selenium and selenium biotransformation. Selection of indigenous selenium tolerant yeast is our goals. The relationship between cell growth and selenium biotransformation was also investigated. Methods: The screening of the yeast cell was carried out at two steps in order to select yeast with high capacity for resistance and accumulation of selenium. The isolates were selected according to produced high biomass at different concentrations of selenium. Secondly, best yeast strains from previous step were grown in presence of 25 mg/L of sodium selenite and organic selenium content was measured. Results: The S17 isolate showed had maximum organic selenium accumulation (2515 ppm) and biomass production (2.73 g/L) compared to the other isolates. The biomass production and organic selenium accumulation of the S17 during 120 hours was shown a direct relationship between growth and biotransformation. Conclusion: This increase in organic selenium content was achieved with yeast screening. It is interesting to know that organic selenium has high bioavailability and low toxicity compared with inorganic selenium. Therefore, finding yeast strains which are resistant to selenium can be very helpful in cancer prevention.

Association between polymorphisms in microRNA seed region and warfarin stable dose.

BACKGROUND: The optimal dose of anticoagulant warfarin varies among patients to achieve the target international normalised ratio. Although genetic variations related to warfarin pharmacokinetics and vitamin K cycle are important factors associated with warfarin dose requirements, these variations do not completely explain the large interindividual variability observed in the most populations, suggesting that additional factors may contribute to this variability. microRNAs have recently been introduced as regulators of drug function genes, and therefore, may be involved in drug responses. In this study, we aimed to evaluate the possible association between variants in the seed region of microRNAs, which target the genes involved in the action of warfarin and warfarin dose requirement. METHODS: 526 samples were collected from Iranian patients. Four selected polymorphisms in the seed region of microRNAs (rs2910164, rs66683138, rs12416605 and rs35770269 in miR-146a, miR-3622a, miR-938 and miR-449c, respectively) were genotyped by PCR-restriction fragment length polymorphism method. RESULTS: rs2910164 C/G in the seed region of miR-146a was associated with warfarin dose requirement (p<0.001); the patients with GG genotype had the higher mean dose of warfarin (40.6 mg/week, compared with 33.9 and 31.8 mg/week for GC and CC genotypes, respectively). The association of other polymorphisms with warfarin dose requirement was not statistically significant. CONCLUSION: rs2910164 C/G in the seed region of miR-146a is associated with warfarin maintenance dose, likely by disrupting interaction between miR-146a and ATP-binding cassette subfamily B member 1 gene, ABCB1. Therefore, this polymorphism may possibly be a potential factor for assessment of warfarin dose requirements.

Association between four microRNA binding site-related polymorphisms and the risk of warfarin-induced bleeding complications.

Bleeding is the most serious complication of warfarin anticoagulation therapy and is known to occur even at patients with therapeutic international normalized ratio (INR) range. Recently, it has been shown that microRNAs play a significant role in pharmacogenetics by regulating genes that are critical for drug function. Interaction between microRNAs and these target genes could be affected by single-nucleotide polymorphisms (SNPs) located in microRNA-binding sites. This study focused on 3'-untranslated region (3'-UTR) SNPs of the genes involved in the warfarin action and the occurrence of bleeding complications in an Iranian population receiving warfarin. A total of 526 patients under warfarin anticoagulation therapy with responding to the therapeutic dose and maintenance of the INR in the range of 2.0-3.5 in three consecutive blood tests were included in the study. Four selected 3'-UTR SNPs (rs12458, rs7294, rs1868774 and rs34669593 located in GATA4, VKORC1, CALU and GGCX genes, respectively) with the potential to disrupt/eliminate or enhance/create microRNA-binding site were genotyped using a simple PCR-based restriction fragment length polymorphism (PCR-RFLP) method. Patients with the rs12458 AT or TT genotypes of the GATA4 gene had a lower risk of bleeding compared to patients with the AA genotype (adjusted OR: 0.478, 95% CI: 0.285-0.802, P= 0.005, OR: 0.416, 95% CI: 0.192-0.902, P= 0.026, respectively). 3'-UTR polymorphisms in other genes were not significantly associated with the risk of bleeding complications. In conclusion, the SNP rs12458A>T in the 3'UTR region of GATA4 is associated with the incidence of warfarin-related bleeding at target range of INR, likely by altering microRNA binding and warfarin metabolism. Further genetics association studies are needed to validate these findings before they can be implemented in clinical settings.