COVID-19 exit strategy during vaccine implementation: a balance between social distancing and herd immunity.

Currently, health authorities around the world are struggling to limit the spread of COVID-19. Since the beginning of the pandemic, social distancing has been the most important strategy used by most countries to control disease spread by flattening and elongating the epidemic curve. Another strategy, herd immunity, was also applied by some countries through relaxed control measures that allow the free spread of natural infection to build up solid immunity within the population. In 2021, COVID-19 vaccination was introduced with tremendous effort as a promising strategy for limiting the spread of disease. Therefore, in this review, we present the current knowledge about social distancing, herd immunity strategies, and aspects of their implementation to control the COVID-19 pandemic in the presence of the newly developed vaccines. Finally, we suggest a short-term option for controlling the pandemic during vaccine application.

Pre-symptomatic and asymptomatic transmission of COVID-19: Implications for control measures in Qatar.

Public health control measures for communicable diseases are often based on the identification of symptomatic cases. However, emerging epidemiological evidence demonstrates the role of pre-symptomatic and asymptomatic transmissions of coronavirus disease 2019 (COVID-19). Understanding high-risk settings where transmissions can occur from infected individuals without symptoms has become critical for improving the response to the pandemic. In this review, we discussed the evidence on the transmission of severe acute respiratory syndrome coronavirus-2, its effect on control strategies, and lessons that can be applied in Qatar. Although Qatar has a small population, it has a distinct setting for COVID-19 control. It has a largely young population and is mostly composed of expatriates particularly from the Middle East and Asia that reside in Qatar for work. Further key considerations for Qatar and travel include population movement during extended religious holiday periods, screening and tracing of visitors and residents at entry points into the country, and expatriates living and working in high-density settings. We also consider how its international airport serves as a major transit destination for the region, as Qatar is expected to experience a rapid expansion of visitors while preparing to host the FIFA World Cup in 2022.

Angiogenin-induced tRNA fragments inhibit translation initiation.

Angiogenin is a stress-activated ribonuclease that cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs). Transfection of natural or synthetic tiRNAs inhibits protein synthesis and triggers the phospho-eIF2α-independent assembly of stress granules (SGs), essential components of the stress response program. We show that selected tiRNAs inhibit protein synthesis by displacing eIF4G/eIF4A from uncapped > capped RNAs. tiRNAs also displace eIF4F, but not eIF4E:4EBP1, from isolated m(7)G cap. We identify a terminal oligoguanine motif that is required to displace the eIF4F complex, inhibit translation, and induce SG assembly. We show that the tiRNA-associated translational silencer YB-1 contributes to angiogenin-, tiRNA-, and oxidative stress-induced translational repression. Our data reveal some of the mechanisms by which stress-induced tRNA cleavage inhibits protein synthesis and activates a cytoprotective stress response program.

Development of gold nanoparticles biosensor for ultrasensitive diagnosis of foot and mouth disease virus.

BACKGROUND: Nano-PCR is a recent tool that is used in viral diseases diagnosis. The technique depends on the fundamental effects of gold nanoparticles (AuNPs) and is considered a very effective and sensitive tool in the diagnosis of different diseases including viral diseases. Although several techniques are currently available to diagnose foot and mouth disease virus (FMDV), a highly sensitive, highly specific technique is needed for specific diagnosis of the disease. In the present work, a novel AuNPs biosensor has been designed using thiol-linked oligonucleotides that recognize the conserved 3D gene of FMDV. RESULTS: The AuNPs-FMDV biosensor specifically recognizes RNA standards of FMDV, but not that of swine vesicular disease virus (SVDV) isolates. The analytical sensitivity of the AuNPs-FMDV biosensor was 10 copy number RNA standards in RT-PCR and 1 copy number RNA standard in real-time rRT-PCR with a 94.5% efficiency, 0.989 R2, a - 3.544 slope and 100% specificity (no cross-reactivity with SVDV). These findings were confirmed by the specific and sensitive recognition of 31 Egyptian FMDV clinical isolates that represents the three FMDV serotypes (O, A, and SAT2). CONCLUSIONS: The AuNPs-FMDV biosensor presents in this study demonstrates a superior analytical and clinical performance for FMDV diagnosis. In addition, this biosensor has a simple workflow and accelerates epidemiological surveillance, hence, it is qualified as an efficient FMDV diagnosis tool for quarantine stations and farms particularly in FMDV endemic areas.

G-quadruplex structures contribute to the neuroprotective effects of angiogenin-induced tRNA fragments.

Angiogenin (ANG) is a stress-activated ribonuclease that promotes the survival of motor neurons. Ribonuclease inactivating point mutations are found in a subset of patients with ALS, a fatal neurodegenerative disease with no cure. We recently showed that ANG cleaves tRNA within anticodon loops to produce 5'- and 3'-fragments known as tRNA-derived, stress-induced RNAs (tiRNAs). Selected 5'-tiRNAs (e.g., tiRNA(Ala), tiRNA(Cys)) cooperate with the translational repressor Y-box binding protein 1 (YB-1) to displace the cap-binding complex eIF4F from capped mRNA, inhibit translation initiation, and induce the assembly of stress granules (SGs). Here, we show that translationally active tiRNAs assemble unique G-quadruplex (G4) structures that are required for translation inhibition. We show that tiRNA(Ala) binds the cold shock domain of YB-1 to activate these translational reprogramming events. We discovered that 5'-tiDNA(Ala) (the DNA equivalent of 5'-tiRNA(Ala)) is a stable tiRNA analog that displaces eIF4F from capped mRNA, inhibits translation initiation, and induces the assembly of SGs. The 5'-tiDNA(Ala) also assembles a G4 structure that allows it to enter motor neurons spontaneously and trigger a neuroprotective response in a YB-1-dependent manner. Remarkably, the ability of 5'-tiRNA(Ala) to induce SG assembly is inhibited by G4 structures formed by pathological GGGGCC repeats found in C9ORF72, the most common genetic cause of ALS, suggesting that functional interactions between G4 RNAs may contribute to neurodegenerative disease.

Influenza a virus host shutoff disables antiviral stress-induced translation arrest.

Influenza A virus (IAV) polymerase complexes function in the nucleus of infected cells, generating mRNAs that bear 5' caps and poly(A) tails, and which are exported to the cytoplasm and translated by host machinery. Host antiviral defences include mechanisms that detect the stress of virus infection and arrest cap-dependent mRNA translation, which normally results in the formation of cytoplasmic aggregates of translationally stalled mRNA-protein complexes known as stress granules (SGs). It remains unclear how IAV ensures preferential translation of viral gene products while evading stress-induced translation arrest. Here, we demonstrate that at early stages of infection both viral and host mRNAs are sensitive to drug-induced translation arrest and SG formation. By contrast, at later stages of infection, IAV becomes partially resistant to stress-induced translation arrest, thereby maintaining ongoing translation of viral gene products. To this end, the virus deploys multiple proteins that block stress-induced SG formation: 1) non-structural protein 1 (NS1) inactivates the antiviral double-stranded RNA (dsRNA)-activated kinase PKR, thereby preventing eIF2α phosphorylation and SG formation; 2) nucleoprotein (NP) inhibits SG formation without affecting eIF2α phosphorylation; 3) host-shutoff protein polymerase-acidic protein-X (PA-X) strongly inhibits SG formation concomitant with dramatic depletion of cytoplasmic poly(A) RNA and nuclear accumulation of poly(A)-binding protein. Recombinant viruses with disrupted PA-X host shutoff function fail to effectively inhibit stress-induced SG formation. The existence of three distinct mechanisms of IAV-mediated SG blockade reveals the magnitude of the threat of stress-induced translation arrest during viral replication.

Novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo.

UNLABELLED: Hepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Here we show an innovative RNA-based targeted approach to enhance endogenous albumin production while reducing liver tumor burden. We designed short-activating RNAs (saRNA) to enhance expression of C/EBPα (CCAAT/enhancer-binding protein-α), a transcriptional regulator and activator of albumin gene expression. Increased levels of both C/EBPα and albumin mRNA in addition to a 3-fold increase in albumin secretion and 50% decrease in cell proliferation was observed in C/EBPα-saRNA transfected HepG2 cells. Intravenous injection of C/EBPα-saRNA in a cirrhotic rat model with multifocal liver tumors increased circulating serum albumin by over 30%, showing evidence of improved liver function. Tumor burden decreased by 80% (P = 0.003) with a 40% reduction in a marker of preneoplastic transformation. Since C/EBPα has known antiproliferative activities by way of retinoblastoma, p21, and cyclins, we used messenger RNA (mRNA) expression liver cancer-specific microarray in C/EBPα-saRNA-transfected HepG2 cells to confirm down-regulation of genes strongly enriched for negative regulation of apoptosis, angiogenesis, and metastasis. Up-regulated genes were enriched for tumor suppressors and positive regulators of cell differentiation. A quantitative polymerase chain reaction (PCR) and western blot analysis of C/EBPα-saRNA-transfected cells suggested that in addition to the known antiproliferative targets of C/EBPα, we also observed suppression of interleukin (IL)6R, c-Myc, and reduced STAT3 phosphorylation. CONCLUSION: A novel injectable saRNA-oligonucleotide that enhances C/EBPα expression successfully reduces tumor burden and simultaneously improves liver function in a clinically relevant liver cirrhosis/HCC model.

Exploiting human CD34+ stem cell-conditioned medium for tissue repair.

Despite the progress in our understanding of genes essential for stem cell regulation and development, little is known about the factors secreted by stem cells and their effect on tissue regeneration. In particular, the factors secreted by human CD34+ cells remain to be elucidated. We have approached this challenge by performing a cytokine/growth factor microarray analysis of secreted soluble factors in medium conditioned by adherent human CD34+ cells. Thirty-two abundantly secreted factors have been identified, all of which are associated with cell proliferation, survival, tissue repair, and wound healing. The cultured CD34+ cells expressed known stem cell genes such as Nanog, Oct4, Sox2, c-kit, and HoxB4. The conditioned medium containing the secreted factors prevented cell death in liver cells exposed to liver toxin in vitro via inhibition of the caspase-3 signaling pathway. More importantly, in vivo studies using animal models of liver damage demonstrated that injection of the conditioned medium could repair damaged liver tissue (significant reduction in the necroinflammatory activity), as well as enable the animals to survive. Thus, we demonstrate that medium conditioned by human CD34+ cells has the potential for therapeutic repair of damaged tissue in vivo.

Correction: Assessing the consistency of iPSC and animal models in cystic fibrosis modelling: A meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0272091.].

Metabolic predictors of COVID-19 mortality and severity: a survival analysis.

Introduction: The global healthcare burden of COVID-19 pandemic has been unprecedented with a high mortality. Metabolomics, a powerful technique, has been increasingly utilized to study the host response to infections and to understand the progression of multi-system disorders such as COVID-19. Analysis of the host metabolites in response to SARS-CoV-2 infection can provide a snapshot of the endogenous metabolic landscape of the host and its role in shaping the interaction with SARS-CoV-2. Disease severity and consequently the clinical outcomes may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. Hence, the host metabolome can help predict potential clinical risks and outcomes. Methods: In this prospective study, using a targeted metabolomics approach, we studied the metabolic signature in 154 COVID-19 patients (males=138, age range 48-69 yrs) and related it to disease severity and mortality. Blood plasma concentrations of metabolites were quantified through LC-MS using MxP Quant 500 kit, which has a coverage of 630 metabolites from 26 biochemical classes including distinct classes of lipids and small organic molecules. We then employed Kaplan-Meier survival analysis to investigate the correlation between various metabolic markers, disease severity and patient outcomes. Results: A comparison of survival outcomes between individuals with high levels of various metabolites (amino acids, tryptophan, kynurenine, serotonin, creatine, SDMA, ADMA, 1-MH and carnitine palmitoyltransferase 1 and 2 enzymes) and those with low levels revealed statistically significant differences in survival outcomes. We further used four key metabolic markers (tryptophan, kynurenine, asymmetric dimethylarginine, and 1-Methylhistidine) to develop a COVID-19 mortality risk model through the application of multiple machine-learning methods. Conclusions: Metabolomics analysis revealed distinct metabolic signatures among different severity groups, reflecting discernible alterations in amino acid levels and perturbations in tryptophan metabolism. Notably, critical patients exhibited higher levels of short chain acylcarnitines, concomitant with higher concentrations of SDMA, ADMA, and 1-MH in severe cases and non-survivors. Conversely, levels of 3-methylhistidine were lower in this context.

CCN3, POSTN, and PTHLH as potential key regulators of genomic integrity and cellular survival in iPSCs.

Reprogramming human somatic cells into a pluripotent state, achieved through the activation of well-defined transcriptional factors known as OSKM factors, offers significant potential for regenerative medicine. While OSKM factors are a robust reprogramming method, efficiency remains a challenge, with only a fraction of cells undergoing successful reprogramming. To address this, we explored genes related to genomic integrity and cellular survival, focusing on iPSCs (A53T-PD1) that displayed enhanced colony stability. Our investigation had revealed three candidate genes CCN3, POSTN, and PTHLH that exhibited differential expression levels and potential roles in iPSC stability. Subsequent analyses identified various protein interactions for these candidate genes. POSTN, significantly upregulated in A53T-PD1 iPSC line, showed interactions with extracellular matrix components and potential involvement in Wnt signaling. CCN3, also highly upregulated, demonstrated interactions with TP53, CDKN1A, and factors related to apoptosis and proliferation. PTHLH, while upregulated, exhibited interactions with CDK2 and genes involved in cell cycle regulation. RT-qPCR validation confirmed elevated CCN3 and PTHLH expression in A53T-PD1 iPSCs, aligning with RNA-seq findings. These genes' roles in preserving pluripotency and cellular stability require further exploration. In conclusion, we identified CCN3, POSTN, and PTHLH as potential contributors to genomic integrity and pluripotency maintenance in iPSCs. Their roles in DNA repair, apoptosis evasion, and signaling pathways could offer valuable insights for enhancing reprogramming efficiency and sustaining pluripotency. Further investigations are essential to unravel the mechanisms underlying their actions.

Stress Factors as Possible Regulators of Pluripotent Stem Cell Survival and Differentiation.

In recent years, extensive research efforts have been directed toward pluripotent stem cells, primarily due to their remarkable capacity for pluripotency. This unique attribute empowers these cells to undergo self-renewal and differentiate into various cell types originating from the ectoderm, mesoderm, and endoderm germ layers. The delicate balance and precise regulation of self-renewal and differentiation are essential for the survival and functionality of these cells. Notably, exposure to specific environmental stressors can activate numerous transcription factors, initiating a diverse array of stress response pathways. These pathways play pivotal roles in regulating gene expression and protein synthesis, ultimately aiming to preserve cell survival and maintain cellular functions. Reactive oxygen species, heat shock, hypoxia, osmotic stress, DNA damage, endoplasmic reticulum stress, and mechanical stress are among the examples of such stressors. In this review, we comprehensively discuss the impact of environmental stressors on the growth of embryonic cells. Furthermore, we provide a summary of the distinct stress response pathways triggered when pluripotent stem cells are exposed to different environmental stressors. Additionally, we highlight recent discoveries regarding the role of such stressors in the generation, differentiation, and self-renewal of induced pluripotent stem cells.

The retrospective study of the metabolic patterns of BCG-vaccination in type-2 diabetic individuals in COVID-19 infection.

Background: The cross-protective nature of Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2 virus was previously suggested, however its effect in COVID-19 patients with type 2 diabetes (T2D) and the underlying metabolic pathways has not been addressed. This study aims to investigate the difference in the metabolomic patterns of type 2 diabetic patients with BCG vaccination showing different severity levels of COVID-19 infection. Methods: Sixty-seven COVID-19 patients were categorized into diabetic and non-diabetic individuals who had been previously vaccinated or not with BCG vaccination. Targeted metabolomics were performed from serum samples from all patients using tandem mass spectrometry. Statistical analysis included multivariate and univariate models. Results: Data suggested that while BCG vaccination may provide protection for individuals who do not have diabetes, it appears to be linked to more severe COVID-19 symptoms in T2D patients (p = 0.02). Comparing the metabolic signature of BCG vaccinated T2D individuals to non-vaccinated counterparts revealed that amino acid (sarcosine), cholesterol esters (CE 20:0, 20:1, 22:2), carboxylic acid (Aconitic acid) were enriched in BCG vaccinated T2D patients, whereas spermidine, glycosylceramides (Hex3Cer(d18:1_22:0), Hex2Cer(d18:1/22:0), HexCer(d18:1/26:1), Hex2Cer(d18:1/24:0), HexCer(d18:1/22:0) were higher in BCG vaccinated non- T2D patients. Furthermore, data indicated a decrease in sarcosine synthesis from glycine and choline and increase in spermidine synthesis in the BCG vaccinated cohort in T2D and non-T2D groups, respectively. Conclusion: This pilot study suggests increased severity of COVID-19 in BCG vaccinated T2D patients, which was marked by decreased sarcosine synthesis, perhaps via lower sarcosine-mediated removal of viral antigens.

Screening and diagnostic testing protocols for HIV and Syphilis infections in health care setting in Qatar: Evaluation and recommendations.

BACKGROUND: HIV and Syphilis are common STIs, which have become a concern and burden on healthcare systems, as many infections go untreated and lead to potentially serious complications. HIV is usually diagnosed with Western blot, PCR, and p24 antigen testing. Whereas, Syphilis is mainly diagnosed through clinical findings and serologic testing. The Medical Commission Department (MC) under MOPH is responsible for screening all newcomers to Qatar, aiming to keep the country free from serious infectious diseases. OBJECTIVE: We aimed to evaluate the diagnostic efficiency of the protocols used in the MC for screening HIV and Syphilis infections. METHODS: We conducted a retrospective study of samples analyzed by 4th Generation ARCHITECT® HIV Ag/Ab Combo and Rapid Plasma Reagin (RPR) between January to December 2019. ARCHITECT® HIV Ag/Ab Combo positive samples were confirmed by INNO-LIA™ HIVI/II and RT-PCR. RPR-reactive samples were confirmed by ARCHITECT® Syphilis Treponema pallidium Antibody (Syphilis TPA) assay. RESULTS: For HIV, data were collected from 585,587 individuals, of which 595 (0.1%) were positive by the ARCHITECT® HIV Ag/Ab Combo (Analyzer A). When all initially positive sera were re-tested on newly collected blood samples using different ARCHITECT® HIV Ag/Ab Combo analyzer (analyzer B), 99.8% (594/595) of samples were also positive, suggesting high reproducibility. The positive predictive value (PPV) between ARCHITECT® HIV Ag/Ab Combo and the INNO-LIA™ HIVI/II confirmatory assay was 31.8%. The PPV between ARCHITECT® HIV Ag/Ab Combo and HIV-PCR assay was 26.8%. Retrospective data for Syphilis were collected from a total of 97,298 individuals who visited the MC, of which 198 (0.20%) were initially positive by RPR. The PPV between RPR and Syphilis TPA confirmatory assay was 36.6%. CONCLUSION: Despite the high rate of false positivity using ARCHITECT® HIV Ag/Ab Combo and RPR screening assays, both assays have proven to be highly effective as screening testing methods.

Influenza prevalence and vaccine efficacy among diabetic patients in Qatar.

Seasonal influenza viruses may lead to severe illness and mortality in patients with comorbidities, including Diabetes Mellitus (DM). Vaccination against influenza in DM patients may reduce influenza incidence and severity. Before the emergence of the COVID-19 pandemic, influenza infections were the most prevalent respiratory infections in Qatar. Still, reports about influenza prevalence and vaccine efficacy in DM patients have not been reported. This study aimed to analyze influenza prevalence among other respiratory infections and assess influenza vaccine efficacy in DM patients in Qatar. Statistical analysis was performed on data obtained from Hamad Medical Corporation (HMC) database for patients that visited the emergency department (ED) with respiratory-like illnesses. The analysis was done for the period between January 2016 to December 2018. Among 17,525 patients who visited HMC-ED with clinical symptoms of respiratory infections, 2611(14.9%) were reported to have DM. Among DM patients, influenza was the most prevalent respiratory pathogen at 48.9%. Influenza virus A (IVA) was the most circulating type, contributing to 38.4%, followed by IVB contributing to 10.4% of total respiratory infections. Among the typed IVA-positive cases, 33.4% were H1N1, and 7.7% were H3N2. A significant decrease in influenza infections was reported in vaccinated DM patients (14.5%) when compared to non-vaccinated patients (18.9%) (p-value = 0.006). However, there was no significant relaxation in the clinical symptoms among vaccinated DM patients compared to their non-vaccinated counterparts. In conclusion, influenza was the most common etiology for respiratory viral infection among diabetic patients at the leading healthcare provider in Qatar. Although vaccination reduced the incidence rate among DM patients, it was less effective in preventing symptoms. Further studies on a larger cohort and for a more extended period are required to investigate influenza prevalence and vaccine efficacy among DM patients.

High-throughput autoantibody screening identifies differentially abundant autoantibodies in autism spectrum disorder.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by defects in two core domains, social/communication skills and restricted/repetitive behaviors or interests. There is no approved biomarker for ASD diagnosis, and the current diagnostic method is based on clinical manifestation, which tends to vary vastly between the affected individuals due to the heterogeneous nature of ASD. There is emerging evidence that supports the implication of the immune system in ASD, specifically autoimmunity; however, the role of autoantibodies in ASD children is not yet fully understood. Materials and methods: In this study, we screened serum samples from 93 cases with ASD and 28 healthy controls utilizing high-throughput KoRectly Expressed (KREX) i-Ome protein-array technology. Our goal was to identify autoantibodies with differential expressions in ASD and to gain insights into the biological significance of these autoantibodies in the context of ASD pathogenesis. Result: Our autoantibody expression analysis identified 29 differential autoantibodies in ASD, 4 of which were upregulated and 25 downregulated. Subsequently, gene ontology (GO) and network analysis showed that the proteins of these autoantibodies are expressed in the brain and involved in axonal guidance, chromatin binding, and multiple metabolic pathways. Correlation analysis revealed that these autoantibodies negatively correlate with the age of ASD subjects. Conclusion: This study explored autoantibody reactivity against self-antigens in ASD individuals' serum using a high-throughput assay. The identified autoantibodies were reactive against proteins involved in axonal guidance, synaptic function, amino acid metabolism, fatty acid metabolism, and chromatin binding.

Hydrogen peroxide induces stress granule formation independent of eIF2α phosphorylation.

In cells exposed to environmental stress, inhibition of translation initiation conserves energy for the repair of cellular damage. Untranslated mRNAs that accumulate in these cells move to discrete cytoplasmic foci known as stress granules (SGs). The assembly of SGs helps cells to survive under adverse environmental conditions. We have analyzed the mechanism by which hydrogen peroxide (H(2)O(2))-induced oxidative stress inhibits translation initiation and induces SG assembly in mammalian cells. Our data indicate that H(2)O(2) inhibits translation and induces the assembly of SGs. The assembly of H(2)O(2)-induced SGs is independent of the phosphorylation of eIF2α, a major trigger of SG assembly, but requires remodeling of the cap-binding eIF4F complex. Moreover, H(2)O(2)-induced SGs are compositionally distinct from canonical SGs, and targeted knockdown of eIF4E, a protein required for canonical translation initiation, inhibits H(2)O(2)-induced SG assembly. Our data reveal new aspects of translational regulation induced by oxidative insults.

Combined Noncoding RNA-mRNA Regulomics Signature in Reprogramming and Pluripotency in iPSCs.

Somatic cells are reprogrammed with reprogramming factors to generate induced pluripotent stem cells (iPSCs), offering a promising future for disease modeling and treatment by overcoming the limitations of embryonic stem cells. However, this process remains inefficient since only a small percentage of transfected cells can undergo full reprogramming. Introducing miRNAs, such as miR-294 and miR302/3667, with reprogramming factors, has shown to increase iPSC colony formation. Previously, we identified five transcription factors, GBX2, NANOGP8, SP8, PEG3, and ZIC1, which may boost iPSC generation. In this study, we performed quantitative miRNAome and small RNA-seq sequencing and applied our previously identified transcriptome to identify the potential miRNA-mRNA regulomics and regulatory network of other ncRNAs. From each fibroblast (N = 4), three iPSC clones were examined (N = 12). iPSCs and original fibroblasts expressed miRNA clusters differently and miRNA clusters were compared to mRNA hits. Moreover, miRNA, piRNA, and snoRNAs expression profiles in iPSCs and original fibroblasts were assessed to identify the potential role of ncRNAs in enhancing iPSC generation, pluripotency, and differentiation. Decreased levels of let-7a-5p showed an increase of SP8 as described previously. Remarkably, the targets of identifier miRNAs were grouped into pluripotency canonical pathways, on stemness, cellular development, growth and proliferation, cellular assembly, and organization of iPSCs.

Assessing the consistency of iPSC and animal models in cystic fibrosis modelling: A meta-analysis.

INTRODUCTION: Cystic fibrosis (CF) is a hereditary autosomal recessive disorder caused by a range of mutations in the CF Transmembrane Conductance Regulator (CFTR) gene. This gene encodes the CFTR protein, which acts as a chloride channel activated by cyclic AMP (cAMP). This meta-analysis aimed to compare the responsiveness of induced pluripotent stem cells (iPSCs) to cAMP analogues to that of commonly used animal models. METHODS: Databases searched included PubMed, Scopus, and Medline from inception to January 2020. A total of 8 and 3 studies, respectively, for animal models and iPSCs, were analyzed. Studies were extracted for investigating cAMP-stimulated anion transport by measuring the short circuit current (Isc) of chloride channels in different animal models and iPSC systems We utilized an inverse variance heterogeneity model for synthesis. RESULTS: Our analysis showed considerable heterogeneity in the mean Isc value in both animal models and iPSCs studies (compared to their WT counterparts), and both suffer from variable responsiveness based on the nature of the underlying model. There was no clear advantage of one over the other. CONCLUSIONS: Studies on both animal and iPSCs models generated considerable heterogeneity. Given the potential of iPSC-derived models to study different diseases, we recommend paying more attention to developing reproducible models of iPSC as it has potential if adequately developed.