ACS Bio Med Chem Au. 2023 Apr 11;3(4):349-358. doi: 10.1021/acsbiomedchemau.2c00089. eCollection 2023 Aug 16.

ABSTRACT

In this work, nanostructured copper materials have been designed, synthetized, and evaluated in order to produce a more efficient and sustainable copper bionanohybrid with catalytical and antimicrobial properties. Thus, conditions are sought where the most critical steps are reduced or minimized, such as the use of reducing agents or the cryogenization step. In addition, the new materials have been characterized through different techniques, and their oxidative and reductive capacities, as well as their antimicrobial activity, have been evaluated. The addition of different quantities of a reducing agent in the synthesis method generated copper bionanohybrids with different metallic species, nanoparticles sizes, and structures. The antimicrobial properties of the bionanohybrids were studied against different strains of Gram-positive and Gram-negative bacteria through two different methods: by counting the CFU and via the disk diffusion test, respectively. The bionanohybrids have demonstrated that different efficiencies depending on the bacterial strain were confronted with. The Cu-PHOS-100% R hybrids with the highest percentage of reduction showed the best antimicrobial efficiency against Escherichia coli and Klebsiella pneumoniae bacteria (>96 or >77% in 4 h, respectively) compared to 31% bacteria reduction using Cu-PHOS-0% R. Also, the antimicrobial activity against Bacillus subtilis materials was obtained with Cu-PHOS-100% R (31 mm inhibition zone and 125 μg/mL minimum inhibitory concentration value). Interestingly, the better antimicrobial activity of the nanobiohybrids against Gram-positive bacteria Mycobacterium smegmatis was obtained with some with a lower reduction step in the synthesis, Cu-PHOS-10% R or Cu-PHOS-20% R (>94% bacterial reduction in 4 h).

PMID:37599792 | PMC:PMC10436259 | DOI:10.1021/acsbiomedchemau.2c00089

J Transl Med. 2023 Aug 20;21(1):558. doi: 10.1186/s12967-023-04435-6.

ABSTRACT

BACKGROUND: Tumor invasiveness reflects numerous biological changes, including tumorigenesis, progression, and metastasis. To decipher the role of transcriptional regulators (TR) involved in tumor invasiveness, we performed a systematic network-based pan-cancer assessment of master regulators of cancer invasiveness.

MATERIALS AND METHODS: We stratified patients in The Cancer Genome Atlas (TCGA) into invasiveness high (INV-H) and low (INV-L) groups using consensus clustering based on an established robust 24-gene signature to determine the prognostic association of invasiveness with overall survival (OS) across 32 different cancers. We devise a network-based protocol to identify TRs as master regulators (MRs) unique to INV-H and INV-L phenotypes. We validated the activity of MRs coherently associated with INV-H phenotype and worse OS across cancers in TCGA on a series of additional datasets in the Prediction of Clinical Outcomes from the Genomic Profiles (PRECOG) repository.

RESULTS: Based on the 24-gene signature, we defined the invasiveness score for each patient sample and stratified patients into INV-H and INV-L clusters. We observed that invasiveness was associated with worse survival outcomes in almost all cancers and had a significant association with OS in ten out of 32 cancers. Our network-based framework identified common invasiveness-associated MRs specific to INV-H and INV-L groups across the ten prognostic cancers, including COL1A1, which is also part of the 24-gene signature, thus acting as a positive control. Downstream pathway analysis of MRs specific to INV-H phenotype resulted in the identification of several enriched pathways, including Epithelial into Mesenchymal Transition, TGF-β signaling pathway, regulation of Toll-like receptors, cytokines, and inflammatory response, and selective expression of chemokine receptors during T-cell polarization. Most of these pathways have connotations of inflammatory immune response and feasibility for metastasis.

CONCLUSION: Our pan-cancer study provides a comprehensive master regulator analysis of tumor invasiveness and can suggest more precise therapeutic strategies by targeting the identified MRs and downstream enriched pathways for patients across multiple cancers.

PMID:37599366 | DOI:10.1186/s12967-023-04435-6

Cell Rep. 2023 Aug 19;42(8):113009. doi: 10.1016/j.celrep.2023.113009. Online ahead of print.

ABSTRACT

To understand how a bacterium ultimately succeeds or fails in adapting to a new host, it is essential to assess the temporal dynamics of its fitness over the course of colonization. Here, we introduce a human-derived commensal organism, Bacteroides thetaiotaomicron (Bt), into the guts of germ-free mice to determine whether and how the genetic requirements for colonization shift over time. Combining a high-throughput functional genetics assay and transcriptomics, we find that gene usage changes drastically during the first days of colonization, shifting from high expression of amino acid biosynthesis genes to broad upregulation of diverse polysaccharide utilization loci. Within the first week, metabolism becomes centered around utilization of a predominant dietary oligosaccharide, and these changes are largely sustained through 6 weeks of colonization. Spontaneous mutations in wild-type Bt also evolve around this locus. These findings highlight the importance of considering temporal colonization dynamics in developing more effective microbiome-based therapies.

PMID:37598339 | DOI:10.1016/j.celrep.2023.113009

Biophys J. 2023 Aug 18:S0006-3495(23)00510-6. doi: 10.1016/j.bpj.2023.08.010. Online ahead of print.

ABSTRACT

Allostery, the transfer of information between distant parts of a macromolecule, is a fundamental feature of protein function and regulation. However, allosteric mechanisms are usually not explained by protein structure, requiring information on correlated fluctuations uniquely accessible to molecular simulation. Existing work to extract allosteric pathways from molecular dynamics simulations has focused on thermodynamic correlations. Here we show how kinetic correlations encode complementary information essential to explain observed variations in allosteric regulation. We applied kinetic and thermodynamic correlation analysis on atomistic simulations of H, K, and NRas isoforms in the apo, GTP, and GDP-bound states of Ras protein, with and without complexing to its downstream effector, Raf. We show that Switch I and Switch II are the primary components of thermodynamic and kinetic allosteric networks, consistent with the key roles of these two motifs. These networks connect the switches to an allosteric loop recently discovered from a crystal structure of HRas. This allosteric loop is inactive in KRas, but is coupled to the hydrolysis arm switch II in NRas and HRas. We find that the mechanism in the latter two isoforms are thermodynamic and kinetic, respectively. Binding of Raf-RBD further activates thermodynamic allostery in HRas and KRas but has limited effect on NRas. These results indicate that kinetic and thermodynamic correlations are both needed to explain protein function and allostery. These two distinct channels of allosteric regulation, and their combinatorial variability, may explain how subtle mutational differences can lead to diverse regulatory profiles among enzymatic proteins.

PMID:37598291 | DOI:10.1016/j.bpj.2023.08.010

BMJ Open Gastroenterol. 2023 Aug;10(1):e001158. doi: 10.1136/bmjgast-2023-001158.

ABSTRACT

OBJECTIVE: Haemorrhoids are one of the most common gastrointestinal and anal diseases. In olive oil and honey propolis, flavonoids have beneficial effects on improving vascular function and decreasing vascular resistance. In this study, we aimed to produce a combination of these two substances in the form of lotions and assess their healing and side effects in comparison with routine treatment, anti-haemorrhoid ointment (containing hydrocortisone and lidocaine).

DESIGN: In this randomised clinical trial study, 86 patients with grade 2 or more haemorrhoid degrees, diagnosed by colonoscopy, were divided into two groups, the case (n=44) and control (n=42). The case group was treated with flavonoid lotion, and the control group was treated with anti-haemorrhoid ointment two times per day for 1 month. Patients were followed weekly with history and physical examination. The data of the two groups were collected before and after the intervention and statistically analysed.

RESULTS: Post-treatment reduction in haemorrhoid grade was significant in the case group (p=0.02). This ratio was insignificant in the control group (p=0.139). Flavonoid lotion (p<0.05) significantly reduced the signs and symptoms of haemorrhoids more than anti-haemorrhoid ointment.

CONCLUSION: According to the results, flavonoid lotion can be an excellent alternative to topical chemical drugs, such as anti-haemorrhoid ointment, in treating haemorrhoid disease. Besides its effectiveness and safety, it can be easily manufactured and widely available to patien.

PMID:37597875 | DOI:10.1136/bmjgast-2023-001158

Water Res. 2023 Jul 28;244:120426. doi: 10.1016/j.watres.2023.120426. Online ahead of print.

ABSTRACT

High rates of CO2 fixation and the genetic potential of various groundwater microbes for autotrophic activity have shown that primary production is an important source of organic C in groundwater ecosystems. However, the contribution of specific chemolithoautotrophic groups such as S-oxidizing bacteria (SOB) to groundwater primary production and their adaptation strategies remain largely unknown. Here, we stimulated anoxic groundwater microcosms with reduced S and sampled the microbial community after 1, 3 and 6 weeks. Genome-resolved metaproteomics was combined with 50at-% 13CO2 stable isotope probing to follow the C flux through the microbial food web and infer traits expressed by active SOB in the groundwater microcosms. Already after 7 days, 90% of the total microbial biomass C in the microcosms was replaced by CO2-derived C, increasing to 97% at the end of incubation. Stable Isotope Cluster Analysis revealed active autotrophs, characterized by a uniform 13C-incorporation of 45% in their peptides, to dominate the microbial community throughout incubation. Mixo- and heterotrophs, characterized by 10 to 40% 13C-incorporation, utilized the primarily produced organic C. Interestingly, obligate autotrophs affiliated with Sulfuricella and Sulfuritalea contained traits enabling the storage of elemental S in globules to maintain primary production under energy limitation. Others related to Sulfurimonas seemed to rapidly utilize substrates for fast proliferation, and most autotrophs further maximized their energy yield via efficient denitrification and the potential for H2 oxidation. Mixotrophic SOB, belonging to Curvibacter or Polaromonas, enhanced metabolic flexibility by using organic compounds to satisfy their C requirements. Time series data spanning eight years further revealed that key taxa of our microcosms composed up to 15% of the microbial groundwater community, demonstrating their in-situ importance. This showed that SOB, by using different metabolic strategies, are able to account for high rates of primary production in groundwater, especially at sites limited to geogenic nutrient sources. The widespread presence of SOB with traits such as S storage, H2 oxidation, and organic C utilization in many aquatic habitats further suggested that metabolic versatility governs S-fueled primary production in the environment.

PMID:37597444 | DOI:10.1016/j.watres.2023.120426

Reprod Biomed Online. 2023 May 3;47(4):103226. doi: 10.1016/j.rbmo.2023.04.017. Online ahead of print.

ABSTRACT

RESEARCH QUESTION: Are TUBB8 gene variations present in Iranian infertile women with oocyte maturation arrest or embryo cleavage arrest?

DESIGN: TUBB8 gene variations were investigated by polymerase chain reaction sequencing on blood samples from 16 women with oocyte maturation arrest and 12 women with cleavage arrest, collectively referred to as the experimental cohort, as well as 56 fertile women as the control group. The Exome Sequencing Project and dbSNP databases and the Genome Aggregation Database were used to search the frequency of corresponding variants. PolyPhen and SIFT were used to conduct in-silico analysis of gene variations and Align-GVGD was used to predict the effect of missense variants on proteins. The homology modelling and structure evaluation of variations was also checked.

RESULTS: Two likely pathogenic variants [c.713C>T (p.Thr238Met), c.1054G>T (p.Ala352Ser)] were identified in patients with oocyte maturation arrest and one likely pathogenic variant [c.G763A, (p.Val255Met)] was identified in a patient with cleavage arrest. These changes were absent in controls.

CONCLUSIONS: Three deleterious variants in TUBB8 related to oocyte maturation arrest or cleavage arrest and infertility were identified. TUBB8 variant screening for patients with oocyte maturation and cleavage arrest is recommended.

PMID:37597348 | DOI:10.1016/j.rbmo.2023.04.017

Daru. 2023 Aug 19. doi: 10.1007/s40199-023-00471-1. Online ahead of print.

ABSTRACT

PURPOSE: COVID-19 strangely kills some youth with no history of physical weakness, and in addition to the lungs, it may even directly harm other organs. Its complex mechanism has led to the loss of any significantly effective drug, and some patients with severe forms still die daily. Common methods for identifying disease mechanisms and drug design are often time-consuming or reductionist. Here, we use a novel holistic systems biology approach to predict its molecular mechanisms (in vitro), significant molecular relations with SARS, and repurpose drugs.

METHODS: We have utilized its relative phylogenic similarity to SARS. Using the available omics data for SARS and the fewer data for COVID-19 to decode the mechanisms and their significant relations, We applied the Cytoscape analyzer, MCODE, STRING, and DAVID tools to predict the topographically crucial molecules, clusters, protein interaction mappings, and functional analysis. We also applied a novel approach to identify the significant relations between the two infections using the Fischer exact test for MCODE clusters. We then constructed and analyzed a drug-gene network using PharmGKB and DrugBank (retrieved using the dgidb).

RESULTS: Some of the shared identified crucial molecules, BPs and pathways included Kaposi sarcoma-associated herpesvirus infection, Influenza A, and NOD-like receptor signaling pathways. Besides, our identified crucial molecules specific to host response against SARS-CoV-2 included FGA, BMP4, PRPF40A, and IFI16.

CONCLUSION: We also introduced seven new repurposed candidate drugs based on the drug-gene network analysis for the identified crucial molecules. Therefore, we suggest that our newly recommended repurposed drugs be further investigated in Vitro and in Vivo against COVID-19.

PMID:37597114 | DOI:10.1007/s40199-023-00471-1

Nature. 2023 Aug 18. doi: 10.1038/s41586-023-06543-1. Online ahead of print.

NO ABSTRACT

PMID:37596490 | DOI:10.1038/s41586-023-06543-1

Br J Cancer. 2023 Aug 18. doi: 10.1038/s41416-023-02395-8. Online ahead of print.

ABSTRACT

BACKGROUND: Intratumor heterogeneity (ITH) in microsatellite instability-high (MSI-H) colorectal cancer (CRC) has been poorly studied. We aimed to clarify how the ITH of MSI-H CRCs is generated in cancer evolution and how immune selective pressure affects ITH.

METHODS: We reanalyzed public whole-exome sequencing data on 246 MSI-H CRCs. In addition, we performed a multi-region analysis from 6 MSI-H CRCs. To verify the process of subclonal immune escape accumulation, a novel computational model of cancer evolution under immune pressure was developed.

RESULTS: Our analysis presented the enrichment of functional genomic alterations in antigen-presentation machinery (APM). Associative analysis of neoantigens indicated the generation of immune escape mechanisms via HLA alterations. Multiregion analysis revealed the clonal acquisition of driver mutations and subclonal accumulation of APM defects in MSI-H CRCs. Examination of variant allele frequencies demonstrated that subclonal mutations tend to be subjected to selective sweep. Computational simulations of tumour progression with the interaction of immune cells successfully verified the subclonal accumulation of immune escape mutations and suggested the efficacy of early initiation of an immune checkpoint inhibitor (ICI) -based treatment.

CONCLUSIONS: Our results demonstrate the heterogeneous acquisition of immune escape mechanisms in MSI-H CRCs by Darwinian selection, providing novel insights into ICI-based treatment strategies.

PMID:37596408 | DOI:10.1038/s41416-023-02395-8

Nat Protoc. 2023 Aug 18. doi: 10.1038/s41596-023-00863-2. Online ahead of print.

ABSTRACT

The production of induced neuronal (iN) cells from human embryonic stem cells (ESCs) and induced pluripotent stem cells by the forced expression of proneural transcription factors is rapid, efficient and reproducible. The ability to generate large numbers of human neurons in such a robust manner enables large-scale studies of human neural differentiation and neuropsychiatric diseases. Surprisingly, similar transcription factor-based approaches for converting mouse ESCs into iN cells have been challenging, primarily because of low cell survival. Here, we provide a detailed approach for the efficient and reproducible generation of functional iN cells from mouse ESC cultures by the genetically induced expression of neurogenin-2. The resulting iN cells display mature pre- and postsynaptic specializations and form synaptic networks. Our method provides the basis for studying neuronal development and enables the direct comparison of cellular phenotypes in mouse and human neurons generated in an equivalent way. The procedure requires 14 d and can be carried out by users with expertise in stem cell culture.

PMID:37596357 | DOI:10.1038/s41596-023-00863-2

ISME Commun. 2023 Aug 18;3(1):78. doi: 10.1038/s43705-023-00297-7.

ABSTRACT

Lytic phages can be potent and selective inhibitors of microbial growth and can have profound impacts on microbiome composition and function. However, there is uncertainty about the biogeochemical conditions under which phage predation modulates microbial ecosystem function, particularly in terrestrial systems. Ionic strength is critical for infection of bacteria by many phages, but quantitative data is limited on the ion thresholds for phage infection that can be compared with environmental ion concentrations. Similarly, while carbon composition varies in the environment, we do not know how this variability influences the impact of phage predation on microbiome function. Here, we measured the half-maximal effective concentrations (EC50) of 80 different inorganic ions for the infection of E. coli with two canonical dsDNA and ssRNA phages, T4 and MS2, respectively. Many alkaline earth metals and alkali metals enabled lytic infection but the ionic strength thresholds varied for different ions between phages. Additionally, using a freshwater nitrate-reducing microbiome, we found that the ability of lytic phages to influence nitrate reduction end-products depended upon the carbon source as well as ionic strength. For all phage:host pairs, the ion EC50s for phage infection exceeded the ion concentrations found in many terrestrial freshwater systems. Thus, our findings support a model where phages most influence terrestrial microbial functional ecology in hot spots and hot moments such as metazoan guts, drought influenced soils, or biofilms where ion concentration is locally or transiently elevated and nutrients are available to support the growth of specific phage hosts.

PMID:37596312 | DOI:10.1038/s43705-023-00297-7

Sci Rep. 2023 Aug 18;13(1):13462. doi: 10.1038/s41598-023-40496-9.

ABSTRACT

Metabolomics has a long history of using cosine similarity to match experimental tandem mass spectra to databases for compound identification. Here we introduce the Blur-and-Link (BLINK) approach for scoring cosine similarity. By bypassing fragment alignment and simultaneously scoring all pairs of spectra using sparse matrix operations, BLINK is over 3000 times faster than MatchMS, a widely used loop-based alignment and scoring implementation. Using a similarity cutoff of 0.7, BLINK and MatchMS had practically equivalent identification agreement, and greater than 99% of their scores and matching ion counts were identical. This performance improvement can enable calculations to be performed that would typically be limited by time and available computational resources.

PMID:37596301 | DOI:10.1038/s41598-023-40496-9

Nat Commun. 2023 Aug 18;14(1):5033. doi: 10.1038/s41467-023-40696-x.

ABSTRACT

The novel coronavirus pandemic (COVID-19) has necessitated a global increase in the use of face masks to limit the airborne spread of the virus. The global demand for personal protective equipment has at times led to shortages of face masks for the public, therefore makeshift masks have become commonplace. The severe acute respiratory syndrome caused by coronavirus-2 (SARS-CoV-2) has a spherical particle size of ~97 nm. However, the airborne transmission of this virus requires the expulsion of droplets, typically ~0.6-500 µm in diameter (by coughing, sneezing, breathing, and talking). In this paper, we propose a face covering that has been designed to effectively capture SARS-CoV-2 whilst providing uncompromised comfort and breathability for the wearer. Herein, we describe a material approach that uses amorphous silica microspheres attached to cotton fibres to capture bioaerosols, including SARS CoV-2. This has been demonstrated for the capture of aerosolised proteins (cytochrome c, myoglobin, ubiquitin, bovine serum albumin) and aerosolised inactivated SARS CoV-2, showing average filtration efficiencies of ~93% with minimal impact on breathability.

PMID:37596260 | DOI:10.1038/s41467-023-40696-x

Small. 2023 Aug 18:e2305026. doi: 10.1002/smll.202305026. Online ahead of print.

ABSTRACT

Ag2 S nanoparticles (NPs) emerge as a unique system that simultaneously features in vivo near-infrared (NIR) imaging, remote heating, and low toxicity thermal sensing. In this work, their capabilities are extended into the fields of optical coherence tomography (OCT), as contrast agents, and NIR probes in both ex vivo and in vivo experiments in eyeballs. The new dual property for ocular imaging is obtained by the preparation of Ag2 S NPs ensembles with a biocompatible amphiphilic block copolymer. Rather than a classical ligand exchange, where surface traps may arise due to incomplete replacement of surface sites, the use of this polymer provides a protective extra layer that preserves the photoluminescence properties of the NPs, and the procedure allows for the controlled preparation of submicrometric scattering centers. The resulting NPs ensembles show extraordinary colloidal stability with time and biocompatibility, enhancing the contrast in OCT with simultaneous NIR imaging in the second biological window.

PMID:37596060 | DOI:10.1002/smll.202305026

Biosystems. 2023 Aug 16:105001. doi: 10.1016/j.biosystems.2023.105001. Online ahead of print.

ABSTRACT

SBcoyote is an open-source cross-platform biochemical reaction viewer and editor released under the liberal MIT license. It is written in Python and uses wxPython to implement the GUI and the drawing canvas. It supports the visualization and editing of compartments, species, and reactions. It includes many options to stylize each of these components. For instance, species can be in different colors and shapes. Other core features include the ability to create alias nodes, alignment of groups of nodes, network zooming, as well as an interactive bird-eye view of the network to allow easy navigation on large networks. A unique feature of the tool is the extensive Python plugin API, where third-party developers can include new functionality. To assist third-party plugin developers, we provide a variety of sample plugins, including, random network generation, a simple auto layout tool, export to Antimony, export SBML, import SBML, etc. Of particular interest are the export and import SBML plugins since these support the SBML level 3 layout and render standard, which is exchangeable with other software packages. Plugins are stored in a GitHub repository, and an included plugin manager can retrieve and install new plugins from the repository on demand. Plugins have version metadata associated with them to make it install plugin updates. Availability: https://github.com/sys-bio/SBcoyote.

PMID:37595778 | DOI:10.1016/j.biosystems.2023.105001

Cell. 2023 Aug 17;186(17):3526-3528. doi: 10.1016/j.cell.2023.07.030.

ABSTRACT

The development of molecular couriers to selectively package, export, and recover RNA molecules within human cells is a significant challenge. In this issue of Cell, Horns et al.1 introduce cellular RNA exporters, termed COURIERs, that package, secrete, and protect RNA cargo and establish the foundation for sophisticated cell-to-cell RNA communication.

PMID:37595562 | DOI:10.1016/j.cell.2023.07.030

Mol Cell. 2023 Aug 17;83(16):2959-2975.e7. doi: 10.1016/j.molcel.2023.07.023.

ABSTRACT

Various hormones, kinases, and stressors (fasting, heat shock) stimulate 26S proteasome activity. To understand how its capacity to degrade ubiquitylated proteins can increase, we studied mouse ZFAND5, which promotes protein degradation during muscle atrophy. Cryo-electron microscopy showed that ZFAND5 induces large conformational changes in the 19S regulatory particle. ZFAND5's AN1 Zn-finger domain interacts with the Rpt5 ATPase and its C terminus with Rpt1 ATPase and Rpn1, a ubiquitin-binding subunit. Upon proteasome binding, ZFAND5 widens the entrance of the substrate translocation channel, yet it associates only transiently with the proteasome. Dissociation of ZFAND5 then stimulates opening of the 20S proteasome gate. Using single-molecule microscopy, we showed that ZFAND5 binds ubiquitylated substrates, prolongs their association with proteasomes, and increases the likelihood that bound substrates undergo degradation, even though ZFAND5 dissociates before substrate deubiquitylation. These changes in proteasome conformation and reaction cycle can explain the accelerated degradation and suggest how other proteasome activators may stimulate proteolysis.

PMID:37595557 | DOI:10.1016/j.molcel.2023.07.023

Curr Opin Genet Dev. 2023 Aug 16;82:102095. doi: 10.1016/j.gde.2023.102095. Online ahead of print.

NO ABSTRACT

PMID:37595408 | DOI:10.1016/j.gde.2023.102095

Cancer Treat Res Commun. 2023 Aug 15;36:100751. doi: 10.1016/j.ctarc.2023.100751. Online ahead of print.

ABSTRACT

INTRODUCTION: In this study, we aimed to elucidate the crosstalk between the Wnt/β-catenin signaling pathway and colorectal cancer (CRC) associated with inflammatory bowel disease (IBD) using a bioinformatics analysis of putative common biomarkers and a systems biology approach.

MATERIALS AND METHODS: The following criteria were used to search the GEO and ArrayExpress databases for terms related to CRC and IBD: 1. The dataset containing the transcriptomic data, and 2. Untreated samples by medications or drugs. A total of 42 datasets were selected for additional analysis. The GEO2R identified the differentially expressed genes. The genes involved in the Wnt signaling pathway were extracted from the KEGG database. Enrichment analysis and miRNA target prediction were conducted through the ToppGene online tool.

RESULTS: In CRC datasets, there were 1168 up- and 998 down-regulated probes, whereas, in IBD datasets, there were 256 up- and 200 down-regulated probes. There were 65 upregulated and 57 downregulated genes shared by CRC and IBD. According to KEGG, there were 166 genes in the Wnt pathway. FriZZled5 (FZD5) was a down-regulated gene in both CRC and IBD, as determined by the intersection of CRC- and IBD-related DEGs with the Wnt pathway. It was also demonstrated that miR-191, miR-885-5p, miR-378a-3p, and miR-396-3p affect the FriZZled5 gene expression.

CONCLUSION: It is possible that increased expression of miR-191 and miR-885-5p, or decreased expression of miR-378a -3p and miR396-3, in IBD and CRC results in decreased expression of the FZD5 gene. Based on the function of this gene, FZD5 may be a potential therapeutic target in IBD that progresses to CRC.

PMID:37595345 | DOI:10.1016/j.ctarc.2023.100751