New long noncoding RNA biomarkers and ceRNA networks on miR-616-3p in colorectal cancer: Bioinformatics-based study.

Background: Cancer development is aided by the role of long noncoding RNAs (lncRNAs) that act as competing endogenous RNAs (ceRNAs) absorbing microRNAs (miRNAs). We aimed to discover a novel regulatory axis in colorectal cancer (CRC) and potential biomarkers based on miR-616-3p. Materials and Methods: The gene expression omnibus database was mined for differentially expressed lncRNAs (DELs) and mRNAs. LncRNAs and mRNAs were predicted using the RegRNA and TargetScan databases. A combination of the ciBioPortal and Ensemble databases was used to locate the mRNAs. Cytoscape 3.7.1-built CeRNA networks. A quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to confirm the expression levels of these RNA molecules. Statistical analyses were implemented by GraphPad Prism 9. Results: qRT-PCR showed (Linc01282, lnc-MYADM-1:1, and Zinc Finger Protein 347 [ZNF347]) were overexpressed whereas, (salt-inducible kinases 1 [SIK1], and miR-616-3p) were down regulated. Conclusion: These results identify unique, unreported lncRNAs as CRC prognostic biomarkers, as well as prospective mRNAs as new treatment targets and predictive biomarkers for CRC. In addition, our study uncovered unexplored ceRNA networks that should be studied further in CRC.

Comment on "A novel super-enhancer-related gene signature predicts prognosis and immune microenvironment for breast cancer".

The primary aim of this study is to critically evaluate and comment on the research presented in the article titled "A Novel Super-Enhancer-Related Gene Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer" by Wu et al. Our specific objectives include assessing the methodology employed by the authors, particularly in regard to the utilization of a super-enhancer-related gene signature for breast cancer prognosis prediction. We propose the necessity of subgroup analysis to effectively address the heterogeneity in breast cancer subtypes, which is crucial for the applicability of the SERGs across diverse breast cancer cases. Additionally, we suggest conducting a more comprehensive immune panel study to deepen the understanding of how the immune microenvironment impacts breast cancer prognosis. Our commentary seeks to provide valuable insights into the strengths and weaknesses of the study, contributing to a more comprehensive understanding of its findings and potential clinical implications.

Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy.

The CRISPR system is a revolutionary genome editing tool that has the potential to revolutionize the field of cancer research and therapy. The ability to precisely target and edit specific genetic mutations that drive the growth and spread of tumors has opened up new possibilities for the development of more effective and personalized cancer treatments. In this review, we will discuss the different CRISPR-based strategies that have been proposed for cancer therapy, including inactivating genes that drive tumor growth, enhancing the immune response to cancer cells, repairing genetic mutations that cause cancer, and delivering cancer-killing molecules directly to tumor cells. We will also summarize the current state of preclinical studies and clinical trials of CRISPR-based cancer therapy, highlighting the most promising results and the challenges that still need to be overcome. Safety and delivery are also important challenges for CRISPR-based cancer therapy to become a viable clinical option. We will discuss the challenges and limitations that need to be overcome, such as off-target effects, safety, and delivery to the tumor site. Finally, we will provide an overview of the current challenges and opportunities in the field of CRISPR-based cancer therapy and discuss future directions for research and development. The CRISPR system has the potential to change the landscape of cancer research, and this review aims to provide an overview of the current state of the field and the challenges that need to be overcome to realize this potential.

Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy.

The advent of iPSCs has brought about a significant transformation in stem cell research, opening up promising avenues for advancing cancer treatment. The formation of cancer is a multifaceted process influenced by genetic, epigenetic, and environmental factors. iPSCs offer a distinctive platform for investigating the origin of cancer, paving the way for novel approaches to cancer treatment, drug testing, and tailored medical interventions. This review article will provide an overview of the science behind iPSCs, the current limitations and challenges in iPSC-based cancer therapy, the ethical and social implications, and the comparative analysis with other stem cell types for cancer treatment. The article will also discuss the applications of iPSCs in tumorigenesis, the future of iPSCs in tumorigenesis research, and highlight successful case studies utilizing iPSCs in tumorigenesis research. The conclusion will summarize the advancements made in iPSC-based tumorigenesis research and the importance of continued investment in iPSC research to unlock the full potential of these cells.

Bioactive chitosan/poly(ethyleneoxide)/CuFe2O4 nanofibers for potential wound healing.

Wound healing is a complex process that often requires intervention to accelerate tissue regeneration and prevent complications. The goal of this research was to assess the potential of bioactive chitosan@poly (ethylene oxide)@CuFe2O4 (CS@PEO@CF) nanofibers for wound healing applications by evaluating their morphology, mechanical properties, and magnetic behavior. Additionally, in vitro and in vivo studies were conducted to investigate their effectiveness in promoting wound healing treatment. The nanoparticles exhibited remarkable antibacterial and antioxidant properties. In the nanofibrous mats, the optimal concentration of CuFe2O4 was determined to be 0.1% Wt/V. Importantly, this concentration did not adversely affect the viability of fibroblast cells, which also identified the ideal concentration. The scaffold's hemocompatibility revealed nonhemolytic properties. Additionally, a wound-healing experiment demonstrated significant migration and growth of fibroblast cells at the edge of the wound. These nanofibrous mats are applied to treat rats with full-thickness excisional wounds. Histopathological analysis of these wounds showed enhanced wound healing ability, as well as regeneration of sebaceous glands and hair follicles within the skin. Overall, the developed wound dressing comprises CuFe2O4 nanoparticles incorporated into CS/PEO nanofibrous mats demonstrating its potential for successful application in wound treatment.

Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation.

The use of nanotechnology has the potential to revolutionize the detection and treatment of cancer. Developments in protein engineering and materials science have led to the emergence of new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers for medicinal purposes have been approved for human trials, only a few have been authorized for clinical use in targeting cancer cells. In this review, we analyze some of the authorized formulations and discuss the challenges of translating findings from the lab to the clinic. This study highlights the various nanocarriers and compounds that can be used for selective tumor targeting and the inherent difficulties in cancer therapy. Nanotechnology provides a promising platform for improving cancer detection and treatment in the future, but further research is needed to overcome the current limitations in clinical translation.

The use of RNA-based treatments in the field of cancer immunotherapy.

Over the past several decades, mRNA vaccines have evolved from a theoretical concept to a clinical reality. These vaccines offer several advantages over traditional vaccine techniques, including their high potency, rapid development, low-cost manufacturing, and safe administration. However, until recently, concerns over the instability and inefficient distribution of mRNA in vivo have limited their utility. Fortunately, recent technological advancements have mostly resolved these concerns, resulting in the development of numerous mRNA vaccination platforms for infectious diseases and various types of cancer. These platforms have shown promising outcomes in both animal models and humans. This study highlights the potential of mRNA vaccines as a promising alternative approach to conventional vaccine techniques and cancer treatment. This review article aims to provide a thorough and detailed examination of mRNA vaccines, including their mechanisms of action and potential applications in cancer immunotherapy. Additionally, the article will analyze the current state of mRNA vaccine technology and highlight future directions for the development and implementation of this promising vaccine platform as a mainstream therapeutic option. The review will also discuss potential challenges and limitations of mRNA vaccines, such as their stability and in vivo distribution, and suggest ways to overcome these issues. By providing a comprehensive overview and critical analysis of mRNA vaccines, this review aims to contribute to the advancement of this innovative approach to cancer treatment.

Immunoinformatic prediction of potential immunodominant epitopes from cagW in order to investigate protection against Helicobacter pylori infection based on experimental consequences.

Helicobacter pylori is a leading cause of stomach cancer and peptic ulcers. Thus, identifying epitopes in H. pylori antigens is important for disease etiology, immunological surveillance, enhancing early detection tests, and developing optimal epitope-based vaccines. We used immunoinformatic and computational methods to create a potential CagW epitope candidate for H. pylori protection. The cagW gene of H. pylori was amplified and cloned into pcDNA3.1 (+) for injection into the muscles of healthy BALB/c mice to assess the impact of the DNA vaccine on interleukin levels. The results will be compared to a control group of mice that received PBS or cagW-pcDNA3.1 (+) vaccinations. An analysis of CagW protein antigens revealed 8 CTL and 7 HTL epitopes linked with AYY and GPGPG, which were enhanced by adding B-defensins to the N-terminus. The vaccine's immunogenicity, allergenicity, and physiochemistry were validated, and its strong activation of TLRs (1, 2, 3, 4, and 10) suggests it is antigenic. An in-silico cloning and immune response model confirmed the vaccine's expression efficiency and predicted its impact on the immune system. An immunofluorescence experiment showed stable and bioactive cagW gene expression in HDF cells after cloning the whole genome into pcDNA3.1 (+). In vivo vaccination showed that pcDNA3.1 (+)-cagW-immunized mice had stronger immune responses and a longer plasmid DNA release window than control-plasmid-immunized mice. After that, bioinformatics methods predicted, developed, and validated the three-dimensional structure. Many online services docked it with Toll-like receptors. The vaccine was refined using allergenicity, antigenicity, solubility, physicochemical properties, and molecular docking scores. Virtual-reality immune system simulations showed an impressive reaction. Codon optimization and in-silico cloning produced E. coli-expressed vaccines. This study suggests a CagW epitopes-protected H. pylori infection. These studies show that the proposed immunization may elicit particular immune responses against H. pylori, but laboratory confirmation is needed to verify its safety and immunogenicity.

Constructing a novel competing Endogenous RNAs network based on NR3C1 and X-linked inhibitor of apoptosis protein genes reveals potential prognostic biomarkers in colorectal cancer.

Background: Long noncoding RNAs (lncRNAs) have been recognized as the main modulatory molecules in various cancers and perform as competing endogenous RNAs (ceRNAs). The nuclear hormone receptor superfamily of ligand-activated transcription factors (NR3C1) regulates numerous proliferative and metabolic processes such as tumorigenesis and metabolic diseases. Furthermore, X-linked inhibitor of apoptosis protein (XIAP) belongs to a family of the inhibitors of apoptosis proteins, is located downstream of the glucocorticoid receptor (GR or NR3C1) pathway, and cooperates with GR to suppress apoptosis. However, the underlying mechanisms of NR3C1 and XIAP in colorectal cancer (CRC) remain mainly unclear. This research aims to clarify the potential RNA biomarkers and to construct a novel ceRNA network in CRC. Materials and Methods: Multistep bioinformatics methods such as Lnc2cancer and miRDB databases were applied to identify candidate lncRNAs and miRNAs. The interaction energy between lncRNAs, NR3C1, and XIAP genes was analyzed by the LncRRIsearch database. Plus, microRNAs and lncRNA were evaluated via the Diana tools database to select microRNAs with the most binding scores. Quantitative reverse transcription-polymerase chain reaction (QRT-PCR) was applied to verify RNA molecules' expression levels and their association with the clinicopathological factors in 30 CRC tissues compared to 30 adjacent tissues. Results: QRT-PCR showed upregulation of KCNQ1OT1, NR3C1, and XIAP and downregulation of miR-421. The ceRNA network was constructed with 17 lncRNAs, 2 mRNAs, and 42 miRNAs. Thus, we explained the potential interactions between KCNQ1OT1 and miR-421 with NR3C1 and XIAP genes. Conclusion: Our study represents potential prognostic biomarkers and a new ceRNA network for further study in CRC.

Virulence factors and antibiotic resistance properties of Streptococcus species isolated from hospital cockroaches.

Hospital cockroaches are probable sources of pathogenic bacteria. The present investigation was performed to assess the antibiotic resistance properties and distribution of virulence factors in the Streptococcus spp. isolated from hospital cockroaches. Six hundred and sixty cockroach samples were collected. Cockroaches were washed with normal saline, and the achieved saline was used for bacterial culture. Isolated Streptococcus spp. were subjected to disk diffusion. The distribution of virulence factors and antibiotic resistance genes were assessed using a polymerase chain reaction. The prevalence of S. pyogenes, S. agalactiae, and S. pneumonia amongst examined samples was 4.82%, 1.66%, and 6.96%, respectively. Cfb (53.93%), cyl (52.8%), scaa (51.68%) and glna (50.56%) were the most commonly detected virulence factors. Pbp2b (71.91%), pbp2x (58.42%), mefA (46.06%), ermB (46.06%) and tetM (46.06%) were the most commonly detected antibiotic resistance genes. Streptococcal spp. harbored the highest prevalence of resistance against tetracycline (80.89%), trimethoprim (65.16%), and penicillin (56.17%). To the best of our knowledge, this is the first prevalence report of virulence factors and antibiotic resistance genes in the Streptococcal spp. isolated from American, German, and oriental hospital cockroaches in Iran. Our findings indicated a certain role for cockroaches in nosocomial pathogens transmission in the hospital environment.

Comparison of therapeutic effects of encapsulated Mesenchymal stem cells in Aloe vera gel and Chitosan-based gel in healing of grade-II burn injuries.

Treatment of burn injuries with Mesenchymal stem cells (MSCs) is a great promise due to their unique properties. As two natural and functional wound dressing, Chitosan and Aloe-Vera gel assist wound regeneration by providing a proper environment. In the current study, we aimed to compare the effect of encapsulated BMSCs in Chitosan-based gel and Aloe-Vera gel on the healing of grade-II burn injuries compared to other groups in the rat. After creation of a 2 × 2 cm grade-II burn on dorsal skin of rats, treatments were performed for each group. The wound closure rate and healing properties were evaluated by histopathological analysis on 7, 14, 21 and, 28 days post-treatment. The expression rate of VEGF, Collagen-I and Collagen-III genes was also assessed on days 3, 7, 14, 21 and 28 performing qRT-PCR. The full wound healing with inconsiderable scar formation was achieved for Aloe-vera/BMSCs and Chitosan/BMSCs group on 28th day post-treatment. Pathological results also demonstrated the highest angiogenesis and granulation tissue formation for Aloe-vera/BMSCs and Chitosan/BMSCs groups respectively. The expression level of VEGF, Collagen-I, and Collagen-III genes was significantly higher in these groups on days 14 and 21, compared to other groups. Results demonstrated the synergistic effect of BMSCs when combined with Chitosan or Aloe-vera gel enhanced the healing process of wound healing more than chitosan gel treatment. Therefore, this gel can be considered as effective approaches for treatment of burn injuries.

Clustered Regularly Interspaced Short Palindromic Repeats System of Genome Engineering in Embryos to Repair Genes.

CRISPR is a powerful gene editing tool for correcting disease-causing mutations. It is becoming more and more evident that CRISPR is a promising approach to treating human genetic diseases. The technologies for adding or removing genes have made significant advances over the past few years and have shown promising potential outcomes. In the current study, we mainly introduce the CRISPR/Cas system and there are several applications in the treatment of genetic diseases, particularly during embryo development.

Effect of the cagW-based gene vaccine on the immunologic properties of BALB/c mouse: an efficient candidate for Helicobacter pylori DNA vaccine.

BACKGROUND: Helicobacter pylori (H. pylori) infect more than half of the world population, and they cause different serious diseases such as gastric carcinomas. This study aims to design a vaccine on the basis of cagW against H. pylori infection. After pcDNA3.1 (+)-cagW-CS-NPs complex is produced, it will be administered into the muscles of healthy BALB/c mice in order to study the effect of this DNA vaccine on the interleukin status of mice, representing its effect on the immune system. After that, the results will be compared with the control groups comprising the administration of cagW-pCDNA3.1 (+) vaccine, the administration of chitosan and the administration of PBS in the muscles of mice. METHODS: The cagW gene of H. pylori was amplified by employing PCR, whose product was then cloned into the pcDNA3.1 (+) vector, and this cloning was confirmed by PCR and BamHI/EcoRV restriction enzyme digestion. CagW gene DNA vaccine was encapsulated in chitosan nanoparticles (pcDNA3.1 (+)-cagW-CS-NPs) using a complex coacervation method. The stability and in vitro expression of chitosan nanoparticles were studied by DNase I digestion and transfection, and the immune responses elicited in specific pathogen-free (SPF) mice by the pcDNA3.1 (+)-cagW-CS-NPs were evaluated. Apart from that, the protective potential pcDNA3.1 (+)-cagW-CS-NPs was evaluated by challenging with H. pylori. RESULTS: The pcDNA3.1 (+)-cagW-CS-NPs comprises cagW gene of H. pylori that is encapsulated in chitosan nanoparticles, produced with good morphology, high stability, a mean diameter of 117.7 nm, and a zeta potential of + 5.64 mV. Moreover, it was confirmed that chitosan encapsulation protects the DNA plasmid from DNase I digestion, and the immunofluorescence assay showed that the cagW gene could express in HDF cells and maintain good bioactivity at the same time. In comparison to the mice immunized with the control plasmid, in vivo immunization revealed that mice immunized with pcDNA3.1 (+)-cagW-NPs showed better immune responses and prolonged release of the plasmid DNA. CONCLUSIONS: This research proves chitosan-DNA nanoparticles as potent immunization candidates against H. pylori infection and paves the way for further developments in novel vaccines encapsulated in chitosan nanoparticles.

Preparation of brushite cements with improved properties by adding graphene oxide.

Background: Brushite (dicalcium phosphate dihydrate, DCPD) cement as a promising bioactive material for bone tissue engineering is widely used to treat defects. However, relatively poor mechanical properties of brushite cement limit its application in loadbearing conditions. The aim of this study is to investigate the effect of graphene oxide (GO) addition to the physical-mechanical-biological properties of brushite cement. Methods: The brushite types of cement were prepared by mixing ß-tricalcium phosphate [ß-TCP, Ca3 (PO4)2] and monocalcium phosphate monohydrate [MCPM, Ca(H2PO4)2. H2O]. GO was introduced at 0, 0.5, 2, and 5 wt.% with the liquid. MG63 cells were cultured on the GO/CPC surfaces to observe various cellular activities and hydroxyapatite (HA) mineralization. Results: Based on our results, GO/CPC composites exhibit improvement in compressive strength compared to pure CPC. New Ca-deficient apatite layer was deposited on the composite surface after immersing immersion in SBF for 7 and 14 days. Field emission scanning electron microscope (FESEM) images indicated that pure and GO incorporated brushite cement facilitates cell adhesion. CPC/GO was slightly toxic to cells such that high concentrations of GO decreased the cell viability. Besides, alkaline phosphatase (ALP) activity of cells was improved compared with the pure CPC. Conclusion: Our results highlight the role of graphene oxide that may have great potential in enabling the utility of graphene-based materials in various biomedical applications.

Molecular characterization, serotypes and phenotypic and genotypic evaluation of antibiotic resistance of the Klebsiella pneumoniae strains isolated from different types of hospital-acquired infections.

Purpose: Virulent and resistant Klebsiella pneumoniae strains are considered as one of the most significant causes of hospital-acquired infections. The present investigation was done to study the distribution of virulence factors, capsule serotypes and phenotypic and genotypic evaluation of antibiotic resistance of the K. pneumoniae strains isolated from hospital-acquired infections. Patients Materials and methods: Two hundred and sixty different types of hospital-acquired infections were collected and cultured. Antibiotic resistance pattern of K. pneumoniae isolates and their molecular characterization were studied using disk diffusion and PCR, respectively. Results: One hundred and fifty out of 260 (44.22%) hospital-acquired infections harbored K. pneumoniae. Urine samples (63.75%) had the highest prevalence of K. pneumoniae, while wound (33.33%) had the lowest. K. pneumoniae strains harbored the highest prevalence of resistance against ampicillin (100%), cefuroxime (100%), amoxicillin/clavulanic acid (95.65%) and ceftazidime (95.52%). FimH-1 (93.04%), traT (92.17%), mrkD (84.34%), and entB (80.86%) were the most commonly detected virulence genes. AcrAB (96.52%) and tolC (85.21%) were the most commonly detected antibiotic resistance genes. Prevalence of ompK35 and ompK36 virulence genes were 75.65% and 79.13%, respectively. Prevalence of K1 and K2-positive serotypes were 27.82% and 6.96%, respectively. Conclusions: High prevalence of resistance against several types of antibiotics and simultaneous presence of some virulence factors and multi-drug resistance genes pose an important public health issue.

Skin tissue engineering: wound healing based on stem-cell-based therapeutic strategies.

Normal wound healing is a dynamic and complex multiple phase process involving coordinated interactions between growth factors, cytokines, chemokines, and various cells. Any failure in these phases may lead wounds to become chronic and have abnormal scar formation. Chronic wounds affect patients' quality of life, since they require repetitive treatments and incur considerable medical costs. Thus, much effort has been focused on developing novel therapeutic approaches for wound treatment. Stem-cell-based therapeutic strategies have been proposed to treat these wounds. They have shown considerable potential for improving the rate and quality of wound healing and regenerating the skin. However, there are many challenges for using stem cells in skin regeneration. In this review, we present some sets of the data published on using embryonic stem cells, induced pluripotent stem cells, and adult stem cells in healing wounds. Additionally, we will discuss the different angles whereby these cells can contribute to their unique features and show the current drawbacks.

Trace of survivin in cancer.

Survivin is one of the most cancer-specific proteins overexpressed in almost all malignancies, but is nearly undetectable in most normal tissues in adults. Functionally, as a member of the inhibitor of apoptosis family, survivin has been shown to inhibit apoptosis and increase proliferation. The antiapoptotic function of survivin seems to be related to its ability to inhibit caspases directly or indirectly. Furthermore, the role of survivin in cell cycle division control is related to its role in the chromosomal passenger complex. Consistent with its determining role in these processes, survivin plays a crucial role in cancer progression and cancer cell resistance to anticancer drugs and ionizing radiation. On the basis of these findings, recently survivin has been investigated intensively as an ideal tumor biomarker. Thus, multiple molecular approaches such as use of the RNA interfering technique, antisense oligonucleotides, ribozyme, and small molecule inhibitors have been used to downregulate survivin regulation and inhibit its biological function consequently. In this review, all these approaches are explained and other compounds that induced apoptosis in different cell lines through survivin inhibition are also reported.

Genotyping and antibiotic resistance properties of Helicobacter pylori strains isolated from human and animal gastric biopsies.

PURPOSE: The present study was done to assess the prevalence rate, antibiotic resistance pattern and genotyping status of the Helicobacter pylori strains isolated from human and animal gastric biopsy samples. PATIENTS AND METHODS: A total of 1,150 gastric biopsy samples were randomly collected from humans (children and adults) and animals (cows, sheep and goats). All samples were subjected to culture, urease test and histopathologic examination. H. pylori isolates were also confirmed using the 16S rRNA gene PCR-amplification. Antibiotic resistance pattern was assessed by the disk diffusion method. Distribution of different genotypes was studied by PCR. RESULTS: The prevalence of H. pylori in gastric biopsy samples which were studied using urease test, culture and histological examination were 57.04%, 55.40% and 60.80%, respectively. Samples that were collected from adult humans (78%) and sheep (70%) had the highest prevalence of H. pylori strains, while those of goats (0.6%) and cows (4%) had the lowest. Findings of the culture method were confirmed using PCR-based amplification of 16S rRNA. Distribution of H. pylori among the gastric ulcers, duodenal ulcers, chronic gastritis gastric cancer and chronic cancer samples were 10.40%, 15.70%, 96.50%, 0.60% and 3.14%, respectively. H. pylori strains harbored the highest prevalence of resistance against ampicillin (74.4%), clarithromycin (63.4%), trimethoprim (61.5%) and metronidazole (61.5%). The most commonly detected genotypes among the H. pylori strains isolated from different types of biopsy samples were cagA (84.79%), vacA m2 (55.95%), vacA s1a (49.84%), cagE (48.58%), iceA1 (47.02%) and iceA2 (47.02%). CONCLUSION: High prevalence of antibiotic resistance and virulent genotypes indicates an important public health issue. Similarities in antibiotic resistance and genotyping pattern of H. pylori strains isolated from humans and animals may show their similar routes of infection.