The roles of lncRNAs and miRNAs in pancreatic cancer: a focus on cancer development and progression and their roles as potential biomarkers.

Pancreatic ductal adenocarcinoma (PDAC) is among the most penetrative malignancies affecting humans, with mounting incidence prevalence worldwide. This cancer is usually not diagnosed in the early stages. There is also no effective therapy against PDAC, and most patients have chemo-resistance. The combination of these factors causes PDAC to have a poor prognosis, and often patients do not live longer than six months. Because of the failure of conventional therapies, the identification of key biomarkers is crucial in the early diagnosis, treatment, and prognosis of pancreatic cancer. 65% of the human genome encodes ncRNAs. There are different types of ncRNAs that are classified based on their sequence lengths and functions. They play a vital role in replication, transcription, translation, and epigenetic regulation. They also participate in some cellular processes, such as proliferation, differentiation, metabolism, and apoptosis. The roles of ncRNAs as tumor suppressors or oncogenes in the growth of tumors in a variety of tissues, including the pancreas, have been demonstrated in several studies. This study discusses the key roles of some lncRNAs and miRNAs in the growth and advancement of pancreatic carcinoma. Because they are involved not only in the premature identification, chemo-resistance and prognostication, also their roles as potential biomarkers for better management of PDAC patients.

Evaluation of bacterial safety approaches of platelet blood concentrates: bacterial screening and pathogen reduction.

This mini-review analyzed two approaches to screening bacterial contamination and utilizing pathogen reduction technology (PRT) for Platelet concentrates (PCs). While the culture-based method is still considered the gold standard for detecting bacterial contamination in PCs, efforts in the past two decades to minimize transfusion-transmitted bacterial infections (TTBIs) have been insufficient to eliminate this infectious threat. PRTs have emerged as a crucial tool to enhance safety and mitigate these risks. The evidence suggests that the screening strategy for bacterial contamination is more successful in ensuring PC quality, decreasing the necessity for frequent transfusions, and improving resistance to platelet transfusion. Alternatively, the PRT approach is superior regarding PC safety. However, both methods are equally effective in managing bleeding. In conclusion, PRT can become a more prevalent means of safety for PCs compared to culture-based approaches and will soon comprehensively surpass culture-based bacterial contamination detection methods.

Immunogenicity and adverse events of the COVID-19 vaccines in healthy and individuals with autoimmune diseases in an Iranian population.

Introduction: Recent studies have proposed various COVID-19 vaccines to control the disease and protect susceptible individuals. However, immunogenicity and safety of COVID-19 vaccines in various populations are not well identified yet. Therefore, this study aimed to elucidate the efficacy and safety of the BBIBP-CorV (Sinopharm) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in healthy subjects and patients with autoimmune diseases.Methods: Study population included 121 healthy subjects and 100 patients with autoimmune diseases. Immunization was performed based on the national vaccination protocols. Of the 221 volunteers, 201 subjects received Sinopharm and 20 cases were vaccinated with Oxford-AstraZeneca. During a 1-year follow-up, the immunogenicity was measured by ELISA before primary vaccination and 1 to 3 months after secondary immunization. Side effects were studied before entering the study and 1 week after the second dose.Results: Vaccination had a positive impact on the induction of immunogenic response (p < .0001). The rates of seropositive vaccine responses were 80% and 75% in subjects vaccinated with the Sinopharm and Oxford-AstraZeneca, respectively. The neutralizing antibody values were significantly higher in subjects with autoimmune diseases than those without autoimmunity (p < .05). The rate of adverse events were 38% and 42% in subjects vaccinated with the Sinopharm and Oxford-AstraZeneca, respectively. The rates of immunogenic responses induced with the Sinopharm and Oxford-AstraZeneca were, respectively, 76% and 81.5% in seropositive subjects, while they were 63.8% and 79.1% in seronegative subjects vaccinated with the Sinopharm and Oxford-AstraZeneca, respectively. Individuals previously infected with SARS-CoV-2 showed a significant reduction in the value of SARS-CoV-2 neutralizing antibodies compared with seronegative subjects (p < .01-.05). Seropositive individuals vaccinated with the Sinopharm had significantly higher the percentages of vaccine-related adverse events than seronegative persons (p < .05). There was no significant difference between seronegative and seropositive individuals vaccinated with the Oxford-AstraZeneca.Conclusion: Our findings revealed that the Sinopharm and Oxford-AstraZeneca vaccines are effective in the production of neutralizing antibodies in healthy subjects and patients with autoimmune disorders undergoing immunosuppressive therapies without considerable reactogenicity.

The application of peroxidase mimetic nanozymes in cancer diagnosis and therapy.

In recent decades, scholarly investigations have predominantly centered on nanomaterials possessing enzyme-like characteristics, commonly referred to as nanozymes. These nanozymes have emerged as viable substitutes for natural enzymes, offering simplicity, stability, and superior performance across various applications. Inorganic nanoparticles have been extensively employed in the emulation of enzymatic activity found in natural systems. Nanoparticles have shown a strong ability to mimic a number of enzyme-like functions. These systems have made a lot of progress thanks to the huge growth in nanotechnology research and the unique properties of nanomaterials. Our presentation will center on the kinetics, processes, and applications of peroxidase-like nanozymes. In this discourse, we will explore the various characteristics that exert an influence on the catalytic activity of nanozymes, with a particular emphasis on the prevailing problems and prospective consequences. This paper presents a thorough examination of the latest advancements achieved in the domain of peroxidase mimetic nanozymes in the context of cancer diagnosis and treatment. The primary focus is on their use in catalytic cancer therapy, alongside chemotherapy, phototherapy, sonodynamic therapy, radiation, and immunotherapy. The primary objective of this work is to offer theoretical and technical assistance for the prospective advancement of anticancer medications based on nanozymes. Moreover, it is anticipated that this will foster the investigation of novel therapeutic strategies aimed at achieving efficacious tumor therapy.

Association of the human platelet antigens polymorphisms with platelet count in patients with COVID-19.

Polymorphism in human platelet antigen (HPA)-1 and HPA-3 (GPIIb/IIIa), HPA-2 (GPIb/IX), HPA-4 (GPIIIa), HPA-5 (GPIa/IIa), & HPA-15 (CD109) was investigated in 86 COVID-19-infected patients with thrombocytopenia (Group A) and 136 COVID-19-infected patients without thrombocytopenia (Group B). HPA genotyping was done by the sequence-specific primers PCR method. Lower HPA-3a and higher HPA-3b (P = 0.028) allele frequencies were seen in Group A than in Group B, and homozygosity for HPA 3b (P = 0.038) alleles was more prevalent in Group A than in Group B. The allele and genotype distributions of the other HPA polymorphic variants were similar between the two groups. Univariate analysis identified the CCGGGC (P = 0.016) combined genotype to be negatively associated & the TCGGGC (P = 0.003) and CCGGGC (P = 0.003) to be positively associated with thrombocytopenia. The frequency of anti-HPA-1a and anti-HPA-3a antibodies was significantly higher in all patients compared to other anti-HPAs antibodies (P < 0.05). These results highlight the role of HPAs in the thrombocytopenia of COVID-19 infected patients. This is the first evidence demonstrating the differential association of the six common HPA gene variants and specific HPA genotype combinations with thrombocytopenia in COVID-19-infected patients.

A review: hemocompatibility of magnetic nanoparticles and their regenerative medicine, cancer therapy, drug delivery, and bioimaging applications.

Nanoparticles have demonstrated noteworthy advancements in the management of various complex medical conditions, particularly cancer. In any case, these particles still harbor the potential to improve medicate conveyance to challenging, hard-to-reach loci. The interactions that occur between nanoparticles and red blood cells during their journey throughout the human body, despite exposure to blood, are still not fully understood. Assessment of the ability of nanoparticles to integrate with blood, characterized as nanoparticle compatibility, has been consistently overlooked and undervalued in its import. This review article investigates the effect of nanoparticles on red blood cells, while examining the compatibility of nanoparticles through the angle of hemolysis. This article discusses the main roles of erythrocytes and also provides an informed interpretation of several mechanisms involved in the interaction of nanoparticles and erythrocytes. Throughout the review, significant emphasis is attributed to the investigation of hemocompatibility studies concerning newly designed nanoparticles to promote their successful translation into clinical application. This review article examines the compatibility of magnetic nanoparticles in various fields, including regenerative medicine, cancer therapy, bioimaging, and drug delivery. Our results show that the chemical composition of the nanoparticle surface is a determining factor in hemocompatibility performance and interaction with blood cells. The surface properties of nanoparticles, namely surface charge, geometry, porosity, and surface functionalities of polymers or specific functional groups, represent key determinants of hemocompatibility.

Evaluation of the antitumor activity of moronecidin (Piscidin)-like peptide in combination with anti-PD-1 antibody against melanoma tumor.

Objectives: Immunotherapy has changed the landscape of oncology over the last decade and has become a standard of care for various cancers. Researchers previously demonstrated that B16-F10 melanoma in C57Bl6 mice is resistant to immune checkpoint inhibitors. The goal of this study was to investigate how anti-PD1 antibodies functioned in combination with a new antimicrobial peptide (AMP) called moronecidin-like peptide (MLP). Materials and Methods: We studied the cytotoxic effect of AMP on the B10-F16 tumor cell line with the MTT experiment. The necrotic and apoptotic cells were determined by Presidium iodide (PI) /Annexin V staining and flow cytometry-based methods. Mice were inoculated subcutaneously with B10-F16 tumor cells in the mammary gland. Each group was sacrificed two weeks after the last injection to examine tumor-specific CD8+ T cell responses using flow cytometry. Results: Annexin V and PI staining assay revealed that MPL significantly induces apoptosis in B16F10 cells. It should be noted that MLP in combination with anti-PD-1 improved antigen-specific T-cell responses synergistically (P=0.01) when compared with respective monotherapy. Furthermore, when compared with the respective monotherapies, combination therapy significantly controlled tumor growth in B10-F16 tumor cells and increased survival rate. Conclusion: Treatments with anti-PD-1 inhibitors alone had only a minor effect on tumor size, whereas combination therapy resulted in significant tumor growth control and increased animal survival. MLP therapy combined with anti-PD-1 antibody improves anti-tumor immune response in addition to inducing tumor cell apoptosis. As a result, the evidence suggests that intratumoral injection of MPL can improve anti-PD-1 antibody antitumor response.

Immunogenicity and safety of the BBIBP-CorV vaccine in patients with autoimmune inflammatory rheumatic diseases undergoing immunosuppressive therapy in a monocentric cohort.

INTRODUCTION: Vaccination plays a fundamental role in mastering the COVID-19 pandemic and protecting vulnerable groups. Persons with autoimmune inflammatory rheumatic diseases (AIIRD) requiring immunosuppressive therapies are prioritized for vaccination. However, data concerning immunogenicity and safety of the BBIBP-CorV vaccine in immunosuppressed patients are not found. This study presents data on the efficacy and safety of the BBIBP-CorV vaccine in immunosuppressed patients compared to healthy controls. METHODS: Study population consisted of 100 healthy controls and 100 patients with AIIRD. Vaccination was performed according to national guidelines with the BBIBP-CorV vaccine. SARS-CoV-2 neutralizing antibody titers were quantified by enzyme-linked immunosorbent assay before initial vaccination and 1-3 months after secondary vaccination. Adverse events were assessed before study initiation and 7 days after the second dose. Disease activity was studied before entering the study and 3-8 weeks after the second dose. RESULTS: Vaccination-induced positive immunogenic response rates and SARS-CoV-2 neutralizing antibody titers were significantly lower in the AIIRD patients than healthy subjects (p < .05). There are significant differences in neutralizing antibody titers among patients suffering from rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis, and ankylosing spondylitis (p < .01-.05). The rates of seropositive vaccine responses were similarly distributed across all diseases. Healthy and AIIRD individuals had a similar profile in adverse events. No significant difference was observed in SARS-CoV-2 antibody titers between subjects suffering from side effects and those who did not have. SARS-CoV-2 neutralizing antibody levels were significantly higher in subjects with a history of COVID-19 infection than seronegative individuals (p < .01-0.05). Seropositive subjects had a significant increase in the percentage of vaccine-related adverse events compared to seronegative persons (p < .05). Despite a minor change in the disease activity of patients with RA and SLE, disease activity indices were overall stable in the AIIRD patients. CONCLUSION: These findings revealed that the BBIBP-CorV vaccine is effective in the development of neutralizing antibodies in immunosuppressed patients without considerable reactogenicity or induction of disease flares.

The use of nanoparticles in the treatment of infectious diseases and cancer, dental applications and tissue regeneration: a review.

The emergence of nanotechnology as a field of study can be traced back to the 1980s, at which point the means to artificially produce, control, and observe matter on a nanometer level was made viable. Recent advancements in technology have enabled us to extend our reach to the nanoscale, which has presented an unparalleled opportunity to directly target biomolecular interactions. As a result of these developments, there is a drive to arise intelligent nanostructures capable of overcoming the obstacles that have impeded the progress of conventional pharmacological methodologies. After four decades, the gradual amalgamation of bio- and nanotechnologies is initiating a revolution in the realm of disease detection, treatment, and monitoring, as well as unsolved medical predicaments. Although a significant portion of research in the field is still confined to laboratories, the initial application of nanotechnology as treatments, vaccines, pharmaceuticals, and diagnostic equipment has now obtained endorsement for commercialization and clinical practice. The current issue presents an overview of the latest progress in nanomedical strategies towards alleviating antibiotic resistance, diagnosing and treating cancer, addressing neurodegenerative disorders, and an array of applications, encompassing dentistry and tuberculosis treatment. The current investigation also scrutinizes the deployment of sophisticated smart nanostructured materials in fields of application such as regenerative medicine, as well as the management of targeted and sustained release of pharmaceuticals and therapeutic interventions. The aforementioned concept exhibits the potential for revolutionary advancements within the field of immunotherapy, as it introduces the utilization of implanted vaccine technology to consistently regulate and augment immune functions. Concurrently with the endeavor to attain the advantages of nanomedical intervention, it is essential to enhance the unceasing emphasis on nanotoxicological research and the regulation of nanomedications' safety. This initiative is crucial in achieving the advancement in medicine that currently lies within our reach.

Gynecologic Cancer, Cancer Stem Cells, and Possible Targeted Therapies.

Gynecologic cancer is one of the main causes of death in women. In this type of cancer, several molecules (oncogenes or tumor suppressor genes) contribute to the tumorigenic process, invasion, metastasis, and resistance to treatment. Based on recent evidence, the detection of molecular changes in these genes could have clinical importance for the early detection and evaluation of tumor grade, as well as the selection of targeted treatment. Researchers have recently focused on cancer stem cells (CSCs) in the treatment of gynecologic cancer because of their ability to induce progression and recurrence of malignancy. This has highlighted the importance of a better understanding of the molecular basis of CSCs. The purpose of this review is to focus on the molecular mechanism of gynecologic cancer and the role of CSCs to discover more specific therapeutic approaches to gynecologic cancer treatment.

Functional Deimmunization of Interferon Beta-1b by Identifying and Silencing Human T Cells Epitopes.

Interferonbeta-1b (IFNß-1b) developed as therapeutic protein for the treatment of multiple sclerosis (MS). Studies have been shown that Long-term usage of this protein can lead to the development of anti-drug antibodies (ADAs) and this phenomenon cause total loss or reduced efficacy of IFNß-1b. The aim of this study was to predict and silence IFNß-1b T-cells epitopes by in silico methods and genetic engineering. Based on bioinformatics studies we identified optimal sets of conservative point mutations for eliminating T-cells epitopes in IFNß-1b protein. Four synthetic genes with desirable mutation constructed and PET26b+ was used as an expression vector in E. coli. The expression of this proteins confirmed by SDS-PAGE and Western blotting, consequently, IFNß-1b proteins was purified by His-tag chromatography. To determined activity of mutants' variants anti-proliferative and anti-viral activity compared to wild form was evaluated using MTT assay in A549 and Vero cells lines respectively. Also the immunogenicity of mutant proteins compared with Betaseron measured in BALB/c mice. The in vitro bioactivity analysis demonstrated that functional activities of all mutant proteins were maintained and is the same as biological activity of Betaseron. Pharmacokinetic studies suggest that, in engineered proteins that contain substitution of Histidine to Glutamic Acid at position 131 (mut 2 and mut 1+2) antibodies response reduced by about 50%, as compared to that for Betaseron. Computational analysis expedites identification and prediction of epitopes in therapeutic protein, therefore, we used immunoinformatic tools for modification of dominant T-cell epitope in IFNß-1b protein, and this strategy has capacity to create proteins which have naturally reduced immunogenicity.

Evaluation of an Albumin-Binding Domain Protein Fused to Recombinant Human IL-2 and Its Effects on the Bioactivity and Serum Half-Life of the Cytokine.

BACKGROUND: Background: Cancer immunotherapy is a promising strategy for cancer treatment. In this strategy, the immune system is triggered to destroy cancer cells. IL-2 is an important factor in passive cancer immunotherapy that helps modulating some important immune functions. One of the IL-2 limitations is low serum half-life; therefore, repetitive high doses of the injections are required to maintain effective concentrations. High-dose IL-2 therapy results in severe side effects; thus, improvement of its serum half-life would provide therapeutic benefits. METHODS: We have investigated a strategy that is able to utilize an albumin-binding domain (ABD) from streptococcal protein G. In this strategy, the fusion protein ABD-rIL-2 binds to serum albumin, which results in improvement of the IL-2 serum half-life. PET26b+ plasmid was used as an expression vector, which encoded rIL-2 and ABD-rIL-2 both fused to pelB secretion signal under the control of the strong bacteriophage T7 promoter. The constructs were expressed in E. coli Rosetta (DE3) and secreted into the periplasm. RESULTS: The analysis of in vitro bioactivity proved that the fusion of ABD to rIL-2 does not interfere with its bioactivity. ABD-rIL-2 fusion protein indicated higher serum half-life compared to rIL-2, when it was tested in the BALB/c mice. CONCLUSION: The current study provides an alternative strategy to extend the half-life and improve pharmacokinetic properties of rIL-2 without reducing its bioactivity in vitro.