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.

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.

An experimental in silico study on COVID-19: Response of neutrophil-related genes to antibiotics.

Background and Aims: All components of the immune system are involved in alleviating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further research is required to provide detailed insights into COVID-19-related immune compartments and pathways. In addition, a significant percentage of hospitalized COVID-19 patients suspect bacterial infections and antimicrobial resistance occurs following antibiotics treatment. The aim of this study was to evaluate the possible effects of antibiotics on the response of neutrophil-related genes in SARS-CoV-2 patients by an experimental in silico study. Methods: The two data sets GSE1739 and GSE21802 including 10 SARS positive patients and 35 influenza A (H1N1) patients were analyzed, respectively. Differentially expressed genes (DEGs) between these two data sets were determined by GEO2R analysis and the Venn diagram online tool. After determining the hub genes involved in immune responses, the expression of these genes in 30 COVID-19 patients and 30 healthy individuals was analyzed by real-time polymerase chain reaction (PCR). All patients received antibiotics, including levofloxacin, colistin, meropenem, and ceftazidime. Results: GEO2R analysis detected 240 and 120 DEGs in GSE21802 and GSE1739, respectively. Twenty DEGs were considered as enriched hub genes involved in immune processes such as neutrophil degranulation, neutrophil activation, and antimicrobial humoral response. The central nodes were attributed to the genes of neutrophil elastase (ELANE), arginase 1 (ARG-1), lipocalin 2 (LCN2), and defensin 4 (DEFA4). Compared to the healthy subjects, the expression of LCN2 and DEFA4 were significantly reduced in COVID-19 patients. However, no significant differences were observed in the ELANE and AGR-1 levels between COVID-19 subjects and the control group. Conclusions: Activation and degranulation of neutrophils were observed mainly in SARS, and H1N1 infection processes and antibiotics administration could affect neutrophil activity during viral infection. It can be suggested that antibiotics can decrease inflammation by restoring the expression of neutrophil-related genes in COVID-19 patients.

Dysregulation of RNA interference components in COVID-19 patients.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus causing severe respiratory illness (COVID-19). This virus was initially identified in Wuhan city, a populated area of the Hubei province in China, and still remains one of the major global health challenges. RNA interference (RNAi) is a mechanism of post-transcriptional gene silencing that plays a crucial role in innate viral defense mechanisms by inhibiting the virus replication as well as expression of various viral proteins. Dicer, Drosha, Ago2, and DGCR8 are essential components of the RNAi system, which is supposed to be dysregulated in COVID-19 patients. This study aimed to assess the expression level of the mentioned mRNAs in COVID-19patients compared to healthy individuals. RESULTS: Our findings demonstrated that the expression of Dicer, Drosha, and Ago2 was statistically altered in COVID-19 patients compared to healthy subjects. Ultimately, the RNA interference mechanism as a crucial antiviral defense system was suggested to be dysregulated in COVID-19 patients.

Isolation and Identification of Two Novel Escherichia coli Bacteriophages and Their Application in Wastewater Treatment and Coliform's Phage Therapy.

BACKGROUND: Phage therapy or use of lytic bacteriophages for eliminating bacterial populations has been developed for several aspects of human affairs such as medicine, agriculture and food industries. OBJECTIVES: The high load of coliforms of treated wastewater effluents that are discharged into the rivers or agricultural lands is a serious concern of the Iran Department of Environment and the reduction of coliforms using phages to overcome this problem is an asset. This research aimed to isolate and identify specific lytic coliphages and investigate their effects on native and standard Escherichia coli strains as well as coliform populations in municipal wastewater. MATERIALS AND METHODS: The wastewater sample was cultured on selective culture media to isolate a native coliform strain and characterized using molecular methods. River water was centrifuged and passed through a 0.45 µm filter and its lytic coliphages were enriched and purified against a native E. coli as well as a standard E. coli strain. Municipal wastewater was treated with isolated lytic coliphages and most probable number (MPN) reduction was examined. RESULTS: E. coli SBSWF27, which is a native strain of E. coli from Isfahan municipal wastewater treatment plant, was isolated and characterized. Also two novel bacteriophages related to Myoviridae and Podoviridae families of bacteriophages from Zayandehrood River (Isfahan, Iran) were isolated. These coliphages had lytic effects on E. coli PTCC1399 and E. coli SBSWF27 as coliform's index. The myovirus had a hexagonal head measuring 27.28 nm and a noncontractile tail measuring 204.5 × 13.63 nm. The podovirus had an oval head measuring 98 × 35 nm and a tail, 14 nm in diameter. The treatment of municipal sewage with the coliphage mixture resulted in a 22-fold decrease of the coliform's MPN from 2400 to 110 after two hours of incubation. CONCLUSIONS: This is the first report on isolation and identification of two novel lytic myovirus and podovirus from Zayandehrood River in Isfahan that had lytic effects on E. coli PTCC1399 and E. coli SBSWF27 strains as well as coliform's population of Isfahan municipal wastewater. We suggest that the use of these lytic coliphages for reduction of coliform's population in sewage could be considered as an effective and simple alternative for costly replacement of instruments and establishments of the old wastewater treatment plants.

PCL-forsterite nanocomposite fibrous membranes for controlled release of dexamethasone.

The well-known treatment of the alveolar bone defects is guided tissue regeneration (GTR). Engineered membranes combined with osteo-differentiation factors have been offered a promising strategy for GTR application. Recently, poly(ε-caprolactone) (PCL)-forsterite (PCL-F) nanocomposite fibrous membranes have been developed. However, PCL-F membranes could not promote bone tissue regeneration. The aim of this research is to encapsulate an osteogenic factor [dexamethasone (DEX)] in PCL-F membranes and evaluate the effects of forsterite nanopowder (particle size = 25-45 nm) and fiber organization on DEX delivery for GTR application. The hypothesis is that the release kinetic and profile of DEX could be controlled through variation of forsterite content (0, 5 and 10 wt%) and fiber arrangement (aligned and random). Results demonstrated while DEX release was sustained over a period of 4 weeks, its kinetic was governed by the membrane architecture and composition. For example, aligned PCL-F nanocomposite fibrous membrane consisting of 10 %(w/v) forsterite nanopowder exhibited the least initial burst release (13 % release in the first 12 h) and allowed sustained release of DEX. Additionally, forsterite nanopowder inclusion changed the kinetic of DEX release from Fickian diffusion to an anomalous transport. The bioactivity of released DEX was estimated using culturing the stem cells from human exfoliated deciduous teeth (SHED) on the membranes. Results demonstrated that proliferation and osteogenic differentiation of SHED could be governed by DEX release process. While DEX release from the membranes decreased SHED proliferation, stimulated the matrix mineralization. Our finding indicated that aligned PCL-F/DEX membrane could be used as a carrier for the sustained release of drugs relevant for GTR trophy.

Detection of torque teno midi virus/small anellovirus (TTMDV/SAV) in chronic cervicitis and cervical tumors in Isfahan, Iran.

Torque teno midi virus and small anellovirus (TTMDV/SAV) are members of the genus Gammatorquevirus within the family Anelloviridae. Cervical cancer is the second most prevalent cancer after breast cancer. The aim of this study was to determine the frequency of infection by these viruses in cervicitis and cervical tumors of women from Isfahan, Iran. Formalin-fixed, paraffin-embedded tissue samples from cervical cancers (n = 42) and cervicitis cases (n = 79) were subjected to nested PCR to identify TTMDV/SAV viral sequences. Of the 42 tumor cases, 22, 18 and 2 were diagnosed as adenocarcinoma, cervical intraepithelial neoplasia and squamous cell carcinoma, respectively. In total, 23 (55%) of the tumor samples were positive for TTMDV/SAV. Of the 79 cervicitis cases, 38 (48%) were also positive for TTMDV/SAV. This is the first report of TTMDV/SAV in cervicitis and cervical tumors of women.